bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccination against Tropical Theileriosis
Authors: PIPANO E. , SHKAP V.
Published: July 2010

Abstract: Theileria annulata, the cause of tropical theileriosis is propagated in cattle with stage‐to‐stage transmission by Hyalomma ticks. Three stages in the life cycle of the parasite‐tick‐derived sporozoites, intramononuclear schizonts, and erythrocytic merozoites‐infect cattle. When cattle are inoculated with schizont‐infected cells, the parasite is transferred from the donor cell to the recipient. The main pathological damage in cattle is induced by the schizont stage. Each development stage of T. annulata elicits a specific immune response. Schizont‐infected lymphoid cells can be grown indefinitely in culture and prolonged cultivation results in loss of virulence. Blood‐derived schizonts induce stronger immunity than culture‐derived schizonts, which suggests that restrictions on the parasite population or antigenic variation occur during prolonged cultivation. The duration of immunity following sporozoite or schizont infections has not yet been determined, but does not appear to be lifelong. The attenuated, culture‐derived anti‐theileria vaccine proved to be safe and effective in prevention of field theileriosis in large enzootic areas.
Improving Egg Production in Two Indigenous Communities through the Adaptation of Management Practices and Local Knowledge: The Results of Participative Research
Authors: RODRIGUES D. L. , LOK R.
Published: July 2010

Abstract:Free‐ranging poultry (FRP) are known to be efficient in the recycling of residues of agroforestry systems. The objective of this paper is to present the results of participative applied research on the improvement of egg production in two indigenous communities in Costa Rica. This involved a dialectic process of adaptation between indigenous knowledge and introduced management practices. We report an increase in egg production through the use of nests and improved diets.
Safety Testing of Needle Free, Jet Injection Devices to Detect Contamination with Blood and Other Tissue Fluids
Authors: SWEAT JAMES M. , ABDY MARK , WENIGER BRUCE G. , HARRINGTON ROBERT , COYLE BERNARD , ABUKNESHA RAM A. , GIBBS E. PAUL J.
Published: July 2010

Abstract: Needle free jet injection guns have been used extensively in both veterinary and human health to deliver both vaccine and drugs, but in recent years, concerns have mounted for their potential to transmit blood borne disease agents among consecutive vaccinates. A Ped‐O‐Jet® type jet injection device was used to deliver serial subcutaneous injections of 0.5 mL saline (as a surrogate for vaccine) into calves and pigs, with intervening ejectates collected in vials to represent what the next vaccinate would have received. An enzyme linked immunosorbant assay was developed to detect species specific albumin as a marker for blood, using calibration standards from known dilutions of bovine or porcine blood. Assay sensitivity of 20 pL/mL corresponded to the estimated minimal chimpanzee infectious dose of 10 pL for hepatitis B virus. The methodology and available results for evaluating the safety of jet injector devices are reported.
Neuroendocrine Regulation of IL‐12 and TNF‐α/IL‐10 Balance: Clinical Implications
Authors: ELENKOV ILIA J. , CHROUSOS GEORGE P. , WILDER RONALD L.
Published: July 2010

Abstract: Interleukin‐12 and tumor necrosis factor (TNF)‐α promote T‐helper (Th) 1 responses and cellular immunity, whereas IL‐10 suppresses Th1 activities and stimulates Th2 and humoral immune responses. Recent evidence indicates that glucocorticoids, norepinephrine, epinephrine, histamine, and adenosine inhibit the production of human IL‐12 and TNF‐α, whereas they do not affect or even stimulate the production of IL‐10. Through this mechanism these neuroendocrine mediators may cause a selective suppression of Th1 responses and a Th2 shift rather than generalized Th suppression. The substantial Th2‐driving force of endogenous stress mediators, as well as histamine and adenosine, can be amplified to a great extent during certain conditions and may play a role in increased susceptibility of the organism to various infections that are normally cleared by Th1 responses. In addition, conditions that contribute to a substantial increase or decrease of local or systemic concentrations of these mediators via modulation of IL‐12, TNFα/IL‐10 balance may also play a role in induction, expression, and progression of certain autoimmune diseases, allergic/atopic reactions, and tumor growth. These conditions include: acute or chronic stress; cessation of chronic stress or chronic hypoactivity of the stress system; severe exercise; serious surgical procedures or traumatic injuries; major burns; severe ischemia or hypoxia; pregnancy and the postpartum period. Thus, better understanding of the neuroendocrine regulation of IL‐12, TNF‐α/IL‐10 balance might help the development of new therapeutic strategies for the treatment of Th1‐ and Th2‐mediated human diseases.
Hypothalamic Mechanisms of Pain Modulatory Actions of Cytokines and Prostaglandin E2
Authors: HORI T. , OKA T. , HOSOI M. , ABE M. , OKA K.
Published: July 2010

Abstract: A decrease and subsequent increase in nociceptive threshold in the whole body are clinical symptoms frequently observed during the course of acute systemic infection. These biphasic changes in nociceptive reactivity are brought about by central signal substances induced by peripheral inflammatory messages. Systemic administration of lipopolysaccharide (LPS) or interleukin‐1β (IL‐1β), an experimental model of acute infection, may mimic the biphasic changes in nociception, hyperalgesia at small doses of LPS, and IL‐1β and analgesia at larger doses. Our behavioral and electrophysiological studies have revealed that IL‐1β in the brain induces hyperalgesia through the actions of prostaglandin E2 (PGE2) on EP3 receptors in the preoptic area and its neighboring basal forebrain, whereas the IL‐1β‐induced analgesia is produced by the actions of PGE2 on EP1 receptors in the ventromedial hypothalamus. An intravenous injection of LPS (10‐100 μg/kg) produced hyperalgesia only during the period before fever develops and was abolished by microinjection of NS‐398 (an inhibitor of cyclooxygenase 2) into the preoptic area, but not into the other areas in the hypothalamus. The hyperalgesia induced by the cytokines PGE2 and LPS may explain the systemic hyperalgesia clinically observed in the early phase of infectious diseases, which probably warns the organisms of infection before the full development of sickness symptoms. The switching of nociception from hyperalgesia to analgesia accompanied by sickness symptoms may reflect changes in the host's strategy for fighting microbial invasion as the disease progresses.
Molecular Mechanisms of Fever and Endogenous Antipyresis
Authors: KOZAK WIESLAW , KLUGER MATTHEW J. , TESFAIGZI JOHANNES , KOZAK ANNA , MAYFIELD KIMBERLY P. , WACHULEC MACIEJ , DOKLADNY KAROL
Published: July 2010

Abstract:This review summarizes recent studies on endogenous antipyretic mechanisms. Fever is the result of a balance between pyrogenic and cryogenic cytokines and hormones. Although there is considerable evidence that fever evolved as a host defense response, it is important that the rise in body temperature not be too high. Many endogenous cryogens or antipyretics that limit the rise in body temperature have been identified during the last 25 years. These include α‐MSH, arginine vasopressin, glucocorticoids, TNF (under certain circumstances), and IL‐10. Most recently, evidence has accumulated that cytochromeP‐450 (P‐450), part of the alternative pathway for arachidonic acid metabolism, plays an important role in reduction of fever and inflammation. Supporting a role forP‐450 in endogenous antipyresis and antiinflammation includes evidence that (1) inducers ofP‐450 reduce fever, (2) inhibitors ofP‐450 cause a larger fever, (3) andP‐450 arachidonic acid metabolites reduce fever.
Contribution of Differently Localized α2‐ and β‐Adrenoceptors in the Modulation of TNF‐α and IL‐10 Production in Endotoxemic Mice
Authors: SZELÉNYI J. , KISS J. P. , PUSKÁS É. , SZELÉNYI M. , VIZI E. S.
Published: July 2010

Abstract: Evidence is presented that the immune response to endotoxemia is under tonic control of the sympathetic nervous system. Adrenergic agents may influence the immune response both directly through α‐ and β‐adrenergic receptors expressed by immunologically competent cells and indirectly via alteration of the endogenous NA level by influencing the activity of release‐regulating presynaptic α2‐adrenoceptors located on the sympathetic nerve terminals. In the immunomodulatory effect of NA/adrenergic drugs, their action on β‐adrenoceptors was dominant, but the considerable role of α‐adrenoceptors on macrophages was also demonstrated. According to our findings, regulation of the ascending wing of the inflammatory response, that is, TNF‐α production, is more sensitive to the adrenoceptor effect, whereas modulation of its deregulation by IL‐10 production also involves some other determining factors.
Increased Sensitivity of the Baroreceptor Reflex after Bacterial Endotoxin
Authors: ROGAUSCH HEINER , VO NGOC‐THINH , DEL REY ADRIANA , BESEDOVSKY HUGO O.
Published: July 2010

Abstract: Lipopolysaccharide (LPS), an endotoxin that elicits the production of several cytokines, induces cardiovascular changes characterized by increased perfusion of immune organs and compensatory sympathetic vasoconstriction in other tissues. We therefore hypothesized that to adapt to altered blood flow distribution following LPS administration, changes in the sensitivity of reflexes that control blood pressure would occur. Our data show that the sensitivity of the baroreceptor reflex increases significantly two and three hours after the intravenous administration of a subpyrogenic dose of the endotoxin. This change in sensitivity that could occur at peripheral or central levels may underlie necessary adjustments of cardiovascular mechanisms during the course of certain immune responses.
The Neuroimmunomodulatory Peptide α‐MSH
Authors: ICHIYAMA TAKASHI , SATO SOICHIRO , OKADA KUNIYUKI , CATANIA ANNA , LIPTON JAMES M.
Published: July 2010

Abstract: Alpha‐melanocyte‐stimulating hormone (α‐MSH), a neuroimmunomodulatory peptide of ancient origin, is known to be involved in the control of host responses. In inflammatory cells, in the periphery and within the central nervous system, α‐MSH modulates the production and action of proinflammatory cytokines. This broad influence occurs via endogenous α‐MSH (melanocortin) receptors. The key to this anti‐inflammatory influence is inhibition of NF‐κB. Indeed α‐MSH inhibits activation of this nuclear factor through preservation of IκBα, which binds to NF‐κB and prevents its migration to the nucleus. Cells transfected with α‐MSH plasmid vector are resistant to challenge with bacterial lipopolysaccharide. The peptide also act on central melanocortin receptors to modulate inflammation in the periphery. In brief, α‐MSH and certain of its fragments such as α‐MSH [11‐13] KPV modulate inflammation via three general actions: direct actions on peripheral host cells; actions on inflammatory cells within the brain to modulate local reactions; and descending neural anti‐inflammatory pathways that control inflammation in peripheral tissues.
The Neuropeptide α‐MSH in Host Defense
Authors: CATANIA ANNA , CUTULI MARIAGRAZIA , GAROFALO LETIZIA , CARLIN ANDREA , AIRAGHI LORENA , BARCELLINI WILMA , LIPTON JAMES M.
Published: July 2010

Abstract: The presence of the ancient peptide a‐melanocyte‐stimulating hormone (α‐MSH) in barrier organs such as gut and skin suggests that this potent anti‐inflammatory molecule may be a component of the innate host defense. In tests of antimicrobial activities, α‐MSH and its fragment KPV showed inhibitory influences against the gram‐positive bacterium Staphylococcus aureus and the yeast Candida albicans. Anti‐tumor necrosis factor and antimicrobial effects of a‐MSH suggest that the peptide might likewise reduce replication of human immunodeficiency virus (HIV). Treatment with α‐MSH reduced HIV replication in chronically and acutely infected human monocytes. At the molecular level, α‐MSH inhibited activation of the transcription factor NF‐κB known to enhance HIV expression. α‐MSH that combines antipyretic, anti‐inflammatory, and antimicrobial effects could be useful in the treatment of disorders in which infection and inflammation coexist.
Role of Neurotransmitter Autoantibodies in the Pathogenesis of Chagasic Peripheral Dysautonomia
Authors: STERIN‐BORDA LEONOR , BORDA ENRI
Published: July 2010

Abstract: Chagas' disease is caused by a parasite, Trypanosoma cruzi, which is widely distributed in South and Central America. Dysautonomias, derangements of sympathetic and parasympathetic nervous system function, are seen fairly often during the chronic course of Chagas' disease. Many infected subjects developed, in the course of the disease, neurogenic cardiomyopathy or digestive damage. Our investigations show the existence of circulating antibodies in Chagas' disease that bind to β‐adrenergic and muscarinic cholinergic receptor (mAChR). The neurotransmitter receptor‐autoantibody interaction triggers in the cells intracellular signal transductions that alter the physiological behavior of the target organs, leading to tissue damage. Moreover, the deposit of autoantibodies behaving as agonists induces desensitization and/or down regulation of the receptors. This in turn can lead to a progressive blockade of them with sympathetic and parasympathetic denervation. Using synthetic peptides for immunoblotting and enzyme immunoassay, we demonstrated that these autoantibodies reacted against the second extracellular loop of the human heart β1 adrenoceptor and M2 cholinoceptor. Also, the corresponding affinity‐purified antipeptide antibodies displayed an agonist‐like activity associated with specific receptor activation. A strong association between circulating antipeptide M2 mAChR autoantibodies and the presence of patients' low heart rate variablity index, bradycardia and cardiac or esophageal autonomic dysfunction in chronic chagasic patients was verified. This fact make these antipeptide antibodies a proper marker of cardiac neoromyopathy and achalasia.
The Peripheral CRH/Urocortin System
Authors: BAMBERGER CHRISTOPH M. , BAMBERGER ANA‐MARIA
Published: July 2010

Abstract:The hypothalmus‐pituitary‐adrenal (HPA) axis and the immune system communicate at multiple levels: On the one hand, immune system‐derived substances, such as interleukin‐1, interleukin‐6, tumor necrosis factor alpha, and leukemia inhibitory factor can stimulate the HPA axis. On the other hand, HPA axis‐derived substances, most importantly glucocorticoids, can modulate the immune response. Furthermore, factors that were originally thought to be restricted to the HPA axis have been found to be expressed by immune cells. Proteins belonging to the CRH (corticotropin‐releasing hormone) family represent important examples of such hormones. In the early 1990s, it was shown that immunoreactive CRH was present at sites of chemically induced inflammation. Administration of anti‐CRH antibodies reduced the degree of inflammation, pointing to a pro‐inflammatory role of “peripheral” CRH. We and others could show that lymphocytes are one source of immunoreactive CRH; however, the antiserum used in our study as well as in previous reports crossreacted with urocortin, a newly discovered member of the CRH family. Using RT‐PCR, we could clearly demonstrate that human lymphocytes expressed urocortin but not CRH mRNA. These results were confirmed by immunocytochemistry, employing urocortin‐ and CRH‐specific antibodies, respectively. The possible functional roles of urocortin expression in the immune system are discussed.
Cytokines and Neurotrophins Interact in Normal and Diseased States
Authors: OTTEN U. , MÄRZ P. , HEESE K. , HOCK C. , KUNZ D. , ROSE‐JOHN S.
Published: July 2010

Abstract: Neurotrophins (NTs) such as nerve growth factor (NGF) as well as cytokines, for example, interleukin‐6 (IL‐6), are communicators between the nervous and immune systems. There is evidence for mutual interactions between NTs and cytokines. Strategies are being developed to elucidate the molecular mechanism/s of interactions and to understand how cytokines are involved in health and disease. Analysis of underlying signaling pathways in glial cells indicates that different transcription factors, such as NF‐κB, cAMP‐responsive‐element binding protein (CREB), and activator protein 1 (AP‐1), are involved in NT induction. IL‐6 and NTs of the NGF family are coexpressed at sites of nerve injury. Interactions of these factors could modulate both neuronal de‐ and regeneration: IL‐6 in conjunction with its soluble IL‐6 receptor induces a specific pattern of NTs in astrocytes in defined brain regions. This indicates that the IL‐6 system mediates a local supply of NTs that participate in diverse CNS functions, such as protection of neurons from insults, neuronal survival, and neuroimmune responses.
Overproduction of IFN‐γ and TNF‐α from Natural Killer (NK) Cells Is Associated with Abnormal NK Reactivity and Cognitive Derangement in Alzheimer's Disease
Authors: SOLERTE S. B. , CRAVELLO L. , FERRARI E. , FIORAVANTI M.
Published: July 2010

Abstract: Alterations of natural killer (NK) function can be involved in the neuroimmune mechanism of neurodegeneration in dementia of the Alzheimer's type (DAT). NK cell cytotoxicity (NKCC) and the generation and release of IFN‐γ and TNF‐α (spontaneous and modulated by IL‐2) from pure NK cells (CD 16+, CD 56+, CD 3−) were studied together with circulating IFN‐γ and TNF‐α levels and cognitive function in 22 old patients with DAT and 15 healthy old subjects. Higher (p < 0.001) IL‐2 modulated NKCC (with IL‐2 50 U/mL and 100 U/mL) was demonstrated in DAT patients (+35% and +99% from baseline) than in healthy subjects (+6% and +76% from baseline). Increased spontaneous and IL‐2‐induced release of IFN‐γ and TNF‐α from NK cells were found in DAT patients compared to healthy subjects (p < 0.001), whereas no difference of serum IFN‐γ and TNF‐α was demonstrated between DAT and control groups. Significant negative correlations among the spontaneous release of IFN‐γ and TNF‐α from NK and the decrease of the score of cognitive function (MMSE) were found in patients with DAT. In conclusion, alterations of NKCC control and NK‐derived cytokine release in DAT could be involved in the neuroinflammatory mechanism related to the progression of neurodegeneration and dementia.
Effects of Preprotachykinin‐I Peptides on Hematopoietic Homeostasis: A Role for Bone Marrow Endopeptidases
Authors: GASCÓN P. , QIAN J. , JOSHI D. D. , TELI T. , HAIDER A. , RAMESHWAR P.
Published: July 2010

Abstract: Hematopoiesis is maintained by “fine‐tuned” regulation among cytokines, neuropeptides, neurotransmitters, and neurotrophic factors. Neurotransmitters, derived from PPT‐I exert immune and hematopoietic regulation. PPT‐I is also expressed locally in bone marrow (BM) stromal cells. PPT‐I peptides induce the production of cytokines in BM cells, resulting in regulation of both committed progenitors (CFU‐GM) and primitive hematopoietic progenitors (CAFC). Both types of progenitors are regulated differently by the two major PPT‐I peptides, SP and NK‐A. Endopeptidases, present in BM cells, can digest SP to produce SP(1‐4) and SP(4‐11). In this study, we investigated the hematopoietic effects of these fragments on CFU‐GM and CAFC. Similar to the two major intact PPT‐I peptides (SP and NK‐A), we observed different hematopoietic effects by SP(1‐4) and SP(4‐11). Whereas SP(1‐4) exerted inhibitory effects on CFU‐GM and CAFC, SP(4‐11) mediated stimulatory effects. Similar to NK‐A, the inhibitory effects of SP(1‐4) can be partly explained by the induction of suppressive cytokines (TGF‐β, TNF‐α, and INF‐γ). Use of antagonists and screening of a dodecapeptide expression library determined that the effects of SP(1‐4) were mediated by NK‐1. These results show that PPT‐I peptides and their endopeptidase‐derived fragments may add to the fine‐tuned regulation on hematopoiesis. Furthermore, PPT‐I may be exerting autoregulation to protect hematopoietic stem cells. These studies have relevance to stem cell protection and BM transplant.
Light and Immunomodulation
Authors: ROBERTS JOAN E.
Published: July 2010

Abstract: The immune system is susceptible to a variety of stresses. Recent work in neuroimmunology has begun to define how mood alteration, stress, the seasons, and daily rhythms can have a profound effect on immune response through hormonal modifications. Central to these factors may be light through an eye‐brain hormonal modulation. In adult primates, only visible light (400‐700 nm) is received by the retina. This photic energy is then transduced and delivered to the visual cortex and, by an alternative pathway, to the supra‐chiasmatic nucleus (SCN), the hypothalamic region that directs circadian rhythm. Visible light exposure also modulates the pituitary and pineal glands, leading to neuroendocrine changes. Melatonin, norepinephrine, and acetylcholine decrease with light activation, whereas cortisol, serotonin, GABA, and dopamine levels increase. The synthesis of vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP), and neuropeptide Y (NPY) in rat SCN has been shown to be modified by light. These induced neuroendocrine changes can lead to alterations in mood and circadian rhythm as well as immune modulation. An alternative pathway for immune modulation by light is through the skin. Visible light (400‐700 nm) can penetrate epidermal and dermal layers of the skin and may directly interact with circulating lymphocytes to modulate immune function. In contrast to visible light, in vivo exposure to UV‐B (280‐320 nm) and UV‐A (320‐400 nm) radiation can alter normal human immune function only by a skin‐mediated response. It is therefore important, when reporting neuroendocrine immune findings, to control the intensity, timing and wavelength of ambient light.
Interleukin‐1β and Thymic Peptide Regulation of Pituitary and Glial Cell Cytokine Expression and Cellular Proliferation
Authors: SPANGELO BRYAN L. , FARRIMOND DERALD D. , POMPILIUS MELISSA , BOWMAN KAY‐LYNN
Published: July 2010

Abstract: Interleukin‐6 (IL‐6) is a B‐cell differentiating and T‐cell activating cytokine that is expressed in T cells, neutrophils, monocytes, macrophages, and mast cells. Because IL‐6 is also synthesized and released by anterior pituitary cells and IL‐6 stimulates pituitary hormone release, this cytokine may serve a paracrine or autocrine role within the pituitary. Interleukin‐1β (IL‐1β) stimulates IL‐6 release from anterior pituitary cells through a mechanism that involves lysophosphatidylcholine (LPC 18:0) generation and protein kinase C activation. In the rat C6 glioma cell line, IL‐1β synergistically stimulates IL‐6 release in the presence of increased intracellular cAMP concentrations. The catecholamines and serotonin also synergistically stimulate IL‐6 release in the presence of IL‐1β. LPC 18:0 synergistically increases IL‐6 release in the presence of norepinephrine, and IL‐1β transiently increases LPC 18:0 formation in C6 cells. Therefore, IL‐1β induction of LPC 18:0 may lead to increases in IL‐6 production via activation of a kinase cascade. The bovine thymic preparation, thymosin fraction 5 (TF5), also stimulates IL‐6 release from C6 glioma cells in a protein kinase C‐dependent manner. Of interest, TF5 inhibits the proliferation of C6 cells, pituitary adenoma MMQ cells, and promyelocytic HL‐60 cells. We suggest that a thymic hormone immune surveillance mechanism may suppress neuroendocrine and hematopoietic tumor formation. Thus, IL‐1b and certain thymic peptides act to increase IL‐6 expression in neuroendocrine cells. The enhanced production of neuroendocrine cytokines may affect hormone secretion, neurotransmission, and the development of certain neurodegenerative disorders (e.g., Alzheimer's disease). The isolation of the active component of TF5 that inhibits neuroendocrine and hematopoietic tumor cell proliferation will provide a potential therapeutic strategy for the treatment of these tumors.
Possible Function of IL‐6 and TNF as Intraadrenal Factors in the Regulation of Adrenal Steroid Secretion
Authors: JUDD ALLAN M. , CALL GERALD B. , BARNEY MICHELLE , McILMOIL CHRISTOPHER J. , BALLS ADAM G. , ADAMS ANDREW , OLIVEIRA GUSTAVO K.
Published: July 2010

Abstract: Interleukin‐6 (il‐6) and tumor necrosis factor α (TNFα) and their mRNAs are present in the human, rat, and bovine adrenal cortex. The release of these cytokines from adrenal cells is regulated by factors that alter adrenal function (e.g., ACTH, angiotensin II, interleukin‐1). IL‐6 and TNF type 1 receptors are also present on adrenocortical cells. Exposure to IL‐6 increases cortisol or corticosterone release from human, bovine, and rat adrenal cells. IL‐6 increases basal and ACTH‐stimulated aldosterone release, but inhibits angiotensin II‐stimulated aldosterone secretion from bovine adrenal cells. IL‐6 increases dehydroepiandrosterone (DHEA) release from human cells, but decreases DHEA secretion from bovine cells. TNFα inhibits corticosterone release from normal rat adrenal cells or fragments, but increases corticosterone release from cholestatic rat adrenal slices. TNFα decreases cortisol release from bovine and fetal human adrenal cells, but increases cortisol release from adult human adrenal cells. TNFα inhibits aldosterone secretion from rat and bovine adrenocortical cells. TNFα does not affect DHEA secretion from fetal human adrenocortical cells, but inhibits basal and ACTH‐stimulated DHEA release from bovine adrenal cell. Because IL‐6 and TNFα are produced in the adrenal gland and modify adrenal steroid secretion, these cytokines may function as intraadrenal factors in the regulation of adrenal steroid secretion.
Gaseous Neuromodulators in the Control of Neuroendocrine Stress Axis
Authors: NAVARRA P. , DELLO RUSSO C. , MANCUSO C. , PREZIOSI P. , GROSSMAN A.
Published: July 2010

Abstract: The gaseous neuromodulator carbon monoxide has been shown to reduce the stimulated release of stress neuropeptides, such as vasopressin and oxytocin, from the rat hypothalamus in vitro, while evidence concerning corticotropin‐releasing hormone is controversial. In vivo studies have been conducted in the rat, inhibiting heme oxygenase activity‐and hence carbon monoxide biosynthesis‐in the central nervous system by means of specific heme oxygenase blockers; these studies showed that basal heme oxygenase activity tends to oppose exaggerated increases in vasopressin secretion following immune‐inflammatory challenges, whereas it favors the normal rise in circulating ACTH which follows footshock. Another gas normally produced in mammalian brains under basal conditions, hydrogen sulfide, also appears to play a role in the control of the hypothalamo‐pituitary‐adrenal axis. Indeed, increases in hydrogen sulfide levels within the hypothalamus, either obtained with hydrogen sulfide‐enriched media or by the addition of the hydrogen sulfide precursor S‐adenosyl‐methionine, are associated with the inhibition of the stimulated release of corticotropin‐releasing hormone from rat hypothalamic explants. Parellel in vivo experiments in the rat under resting conditions and after stress‐induced adrenocortical activation show that S‐adenosyl‐methionine significantly reduces the rise in serum corticosterone levels caused by 1‐h exposure to cold. These results demonstrate the pathophysiological importance of both carbon monoxide and hydrogen sulfide in the regulation of neuroendocrine function.
Gender, Neuroendocrine‐Immune Interactions and Neuron‐Glial Plasticity: Role of Luteinizing Hormone‐Releasing Hormone (LHRH)
Authors: MARCHETTI BIANCA , GALLO FRANCESCO , FARINELLA ZELINDA , TIROLO CATALDO , TESTA NUCCIO , CANIGLIA SALVO , MORALE MARIA C.
Published: July 2010

Abstract: Signals generated by the hypothalamic‐pitutary‐gonadal (HPG) axis powerfully modulate immune system function. This article summarizes some aspects of the impact of gender in neuroendocrine immunomodulation. Emphasis is given to the astroglial cell compartment, defined as a key actor in neuroendocrine immune communications. In the brain, the principal hormones of the HPG axis directly interact with astroglial cells. Thus, Luteinizing hormone releasing hormone, LHRH, Influences hypothalamic astrocyte development and growth, and hypothalamic astrocytes direct LHRH Neuron differentiation. Hormonally induced changes in neuron‐glial plasticity may Dictate major changes in CNS Output, and thus Actively participate in sex dimorphic immune Responses. THE Impact of gender in Neuroimmunomodulation is further underlined by The sex dimorphism in the expression of genes Encoding for neuroendocrine hormones and their Receptors within the thymus, and by the potent Modulation exerted by circulating sex steroids During development and immunization. the central Role of glucocorticoids in the interactive communication between neuroendocrine and immune systems, And the impact of gender on hypothalamic‐pituitary‐adrenocortical (HPA) axis modulation is Underscored in transgenic mice expressing a glucocorticoid receptor antisense RNA.
The Thymus at the Crossroad of Neuroimmune Interactions
Authors: MARODER MARELLA , BELLAVIA DIANA , VACCA ALESSANDRA , FELLI MARIA PIA , SCREPANTI ISABELLA
Published: July 2010

Abstract: The numerous relationships existing between the nervous and the immune systems suggest that the neural networks present in the intrathymic microenvironment may influence T‐cell development. We previously reported that thymic neural‐crest‐derived stromal cells are involved in a neural differentiation pathway and are able to produce neurotrophic factors and neurokines that are in turn able to increase and/or modulate thymic‐stromal cell neuronal phenotype. We also showed that EGF promotes a neural phenotype in thymic epithelial cells by enhancing the expression of neuronal‐specific markers, neurotransmitters, and neuropoietic cytokines, such as IL‐6 and CNTF. More recently we showed that the effect of EGF in directing thymic epithelial cells toward a neural‐oriented cell fate is mediated by modulating the expression of genes directly involved in neurotypic differentiation (i.e., thrombospondin‐1). EGF‐induced regulation of stromal cells may also affect T‐cell differentiation, as we observed that an EGF‐pretreatment reduces the ability of thymic epithelial cells to sustain thymocyte differentiation in vitro. Finally, we demonstrated that a complex network involving the neurotrophin BDNF and its specific receptors may have a role in sustaining thymocyte precursor survival and supporting the thymocyte differentiation process. All toghether, our results suggest that the thymus may be the site of integration of different neuroimmune networks that are potentially involved in the regulation of thymocyte survival and/or differentiation.
The Opioid Antagonist Naloxone Induces a Shift from Type 2 to Type 1 Cytokine Pattern in Normal and Skin‐Grafted Mice
Authors: SACERDOTE PAOLA , GASPANI LEDA , PANERAI ALBERTO E.
Published: July 2010

Abstract: Opioid peptides affect different immune functions. We present evidence that these effects could be mediated by the modulation of TH1/TH2 cytokine production. The acute and chronic treatment with the opioid receptor antagonist naloxone decreased the production of IL‐4 by splenocytes of C57BL/6 and BALB/CJ mice, that present a Th1/ Th2 dominance, respectively, immunized with the protein antigen KLH. In contrast, IL‐2 and IFN‐γ levels were increased after naloxone treatment. These results indicate that naloxone increases Th1 and decreases Th2 cytokine production. Moreover in C57BL/6 mice, naloxone treatment was able to accelerate skin‐graft rejection, a Th1‐mediated phenomenon, by increasing Th1 cytokine production. The effect of naloxone could be ascribed to the removal of the regulatory effects exerted by endogenous opioid peptides, which could activate Th2 and suppress Th1 cytokines.
Acute Effects of Morphine on Blood Lymphocyte Proliferation and Plasma IL‐6 Levels
Authors: HOUGHTLING RICHARD A. , MELLON R. DANIEL , TAN RODERICK J. , BAYER BARBARA M.
Published: July 2010

Abstract:Administration of morphine (10 mg/kg) to rats was found to decrease the proliferative potential of blood lymphocytes by 60‐80% and concurrently elevate circulating levels of the cytokine, interleukin‐6 (IL‐6), 2‐ to 4‐fold. Both parameters were similarly altered upon the central administration of morphine and were blocked upon pretreatment of animals with the opioid receptor antagonist, naltrexone. These results suggest that the activation of central opioid receptors is involved in morphine‐induced inhibition of lymphocyte proliferation as well as increases in circulating levels of IL‐6. Studies addressing the potential peripheral mechanisms demonstrated that intact ganglionic transmission was required for both effects of morphine. Although the suppression by morphine of lymphocyte proliferation appeared to be largely independent of stimulation of the hypothalamic‐pituitary‐adrenal axis, the elevation of IL‐6 was completely abolished in adrenalectomized animals. collectively, these results suggest that central opioid receptor activation results in changes in different immune parameters that can be mediated through distinct peripheral mechanisms.
Neuroendocrine Manifestations in Sjögren's Syndrome: Relation to the Neurobiology of Stress
Authors: JOHNSON ELIZABETH O. , MOUTSOPOULOS HARALAMPOS M.
Published: July 2010

Abstract: Evidence suggests that autoimmune rheumatic diseases are associated with neuroendocrine dysfunction. Sjögren's syndrome (SS) is proposed as an ideal model to study perturbations in the neuroimmune axis, since patients tend to be medication free and studies are not confounded by the effects of chronic immunosuppressive therapy. The functional integrity of the adrenal, gonadal, and thyroid axes was assessed in SS. Pituitary function of the HPA axis was evaluated directly by determining the acth released during oCRH stimulation, while adrenal function was assessed indirectly by endogenous acth released during ocrh stimulation. Low basal activity of the HPA axis was associated with pituitary hyporesponsiveness to exogenous CRH, as well as hyporesponsiveness of the adrenal glands to endogenous ACTH. These findings are compatible with a central deficiency of the adrenal axis. An overall attenuated and delayed LH and FSH response to LHRH stimulation was also indicative of central dysfunction of the gonadal axis in SS. SS patients demonstrated elevated basal TSH levels and evidence of mild hypothyroidism. basal prolactin concentrations were also elevated in SS, and both TSH and PRL showed relatively increased responses to TRH stimulation. the data suggest a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thyroid. it is not clear if any one system plays a primary role in the expression of the disease. rather, it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones. taken together, adrenal and gondadal steroid hormone deficiency, plus elevated PRL levels, probably greatly affect immune function in SS patients.
Perturbations of Arginine Vasopressin Secretion during Inflammatory Stress: Pathophysiologic Implications
Authors: CHIKANZA IAN C. , PETROU PETROS , CHROUSOS GEORGE
Published: July 2010

Abstract: Pro‐inflammatory cytokines, such as interleukin‐1β (IL‐1β, interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNFα), released from inflammatory foci, can activate the hypothalamus to produce corticotrophin‐releasing hormone (CRH) and arginine vasopressin (AVP). These hypothalamic peptides in synergy increase ACTH production by the pituitary gland and hence corticosteroid (CS) secretion by the adrenal cortices. CS dampens inflammation. The pituitary also produces prolactin (PRL), which is pro‐inflammatory, and macrophage inhibitory factor (MIF), which by counteracting the anti‐inflammatory and immunosuppressive effects of CS, is pro‐inflammatory. Lewis rats develop a variety of induced‐autoimmune inflammatory conditions, such as streptococcal cell wall arthritis, whereas the histocompatible F344 Fisher rats are resistant to this condition. Lewis rats have a defective hypothalamic‐pituitary adrenal (HPA) response to a variety of hypothalamic stimuli, but have augmented systemic secretion of AVP. Patients with rheumatoid arthritis (RA) have deficient CS with exaggerated PRL responses to inflammatory stimuli. Within inflammatory foci, CRH is pro‐inflammatory. AVP, which augments autologous mixed lymphocyte reactions, can replace the IL‐2 requirement for γIFN production by T cells via V1a receptors, and potentiates primary antibody responses, is also pro‐inflammatory. Lewis rats have significantly high plasma levels, hypothalamic content, and in vitro release of AVP in comparison to the inflammatory disease‐resistant Fischer rats. Immunoneutralization of AVP attenuates inflammatory responses. In Sprague‐Dawley rats, AVP potentiates PRL secretion. Preliminary studies in patients with RA have shown that the circulating levels of AVP are significantly increased, which might be a compensatory response to low CS levels or a result of elevated levels of IL‐6 in these patients but could nevertheless contribute to rheumatoid inflammation. A similar observation has been made in patients with ankylosing spondylitis.
The Hypothalamic‐Pituitary‐Adrenal and Gonadal Axes in Rheumatoid Arthritis
Authors: CUTOLO MAURIZIO , VILLAGGIO BARBARA , FOPPIANI LUCA , BRIATA MELANIA , SULLI ALBERTO , PIZZORNI CARMEN , FAELLI FRANCESCA , PRETE CAMILLA , FELLI LAMBERTO , SERIOLO BRUNO , GIUSTI MASSIMO
Published: July 2010

Abstract: The hypothalamic‐pituitary‐adrenal (HPA) and the hypothalamic‐pituitary‐gonadal (HPG) axes involvement or response to immune activation seems crucial for the control of excessive inflammatory and immune conditions such as autoimmune rheumatic diseases, including rheumatoid arthritis (RA). However, female patients seem to depend more on the HPA axis, whereas male patients seem to depend more on the HPG axis. In particular, hypoandrogenism may play a pathogenetic role in male RA patients because adrenal and gonadal androgens, both products of the HPA and HPG axes, are considered natural immunosuppressors. A significantly altered steroidogenesis of adrenal androgens (i.e., dehydroepiandrosterone sulfate, DHEAS and DHEA) in nonglucocorticoid‐treated premenopausal RA patients has been described. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1‐type immunity). A range of physical and psychosocial stressors are also implicated in the activation of the HPA axis and related HPG changes. Chronic and acute stressors appear to have different actions on immune mechanisms with experimental and human studies indicating that acute severe stressors may be even immunosuppressive, while chronic stress may enhance immune responses. The interactions between the immunological and neuroendocrine circuits is the subject of active and extensive ongoing research and might in the near future offer highly promising strategies for hormone‐replacement therapies in RA.
CNS Penetration by Noninvasive Viruses Following Inhalational Anesthetics
Authors: BEN‐NATHAN D. , KOBILER D. , RZOTKIEWICZ S. , LUSTIG S. , KATZ Y.
Published: July 2010

Abstract: The effects of inhalational anesthetics on brain penetration by the neurovirulent noninvasive West Nile virus (WN‐25) were studied in mice. WN‐25 injected intracerebrally causes encephalitis and kills adult mice, but when injected intraperitoneally (i.p.) it is unable to invade the brain and kill. under stress conditions, this strain causes encephalitis and death even after i.p. inoculation. in the study described in this paper, we used two inhalational anesthetics, a single short‐term exposure to 2% halothane for 10 min in oxygen, or 70% nitrous oxide (N2O) for 30 min in air. both inhalational anesthetics induced WN‐25 encephalitis and death in 33% and 20% of the tested mice, respectively. Exposure of inoculated mice to halothane for prolonged periods or for repeated exposures (two or three times) markedly increased the mortality rate (up to 75%). Exposure to 30% CO2, a known modulator of blood‐brain barrier (BBB) activity, was used as a positive control (80% mortality). No death was observed in the control non‐exposed injected mice. Virus levels were found to be more than 107 plaque‐forming units (PFU)/brain in all moribund mice. Additional parameter demonstrating the “stressor‐like” nature of inhalation anesthetics was the induction of a significant decrease in weight of the lymphoid organs of inoculated mice. We suggest that inhalational anesthetics induces BBB breaching with subsequent entrance of the noninvasive WN‐25 virus into the brain, causing encephalitis and death.
Genital Tract Infections and Perinatal Transmission of HIV
Authors: TAHA TAHA E. , GRAY RONALD H.
Published: July 2010

Abstract: In areas of the world where genital tract infections (GTIs) are common, the prevalence of HIV and the rate of mother‐to‐child transmission (MTCT) of HIV are also high. Although observational studies suggested that GTIs are associated with MTCT of HIV, no controlled clinical trial has confirmed this finding. It is likely that GTIs that cause either discharges or ulcers during pregnancy increase perinatal transmission of HIV. Several potential biological mechanisms might facilitate perinatal transmission. For example, chorioamnionitis, increased viral shedding in cervicovaginal secretions, increased HIV acquisition during pregnancy, inflammatory cytokine production, preterm labor, prolonged rupture of membranes, ascending infection, and increased intrapartum infectious secretions are factors that can be associated with GTIs. Several studies have shown that treating clinical conditions associated with inflammation might alter HIV shedding. It is conceivable that preventing ascending infection or reducing exposure of the infant to infectious material during birth could reduce MTCT. This can possibly be achieved by antimicrobial therapy during pregnancy and intrapartum. Such an approach is practical, is less expensive, and has secondary benefits related to prevention of adverse pregnancy outcomes associated with GTIs. Antibiotics might also complement reductions in MTCT of HIV obtained by antiretrovirals given to the mother around the time of delivery. In addition, antibiotics could reduce infectious causes of morbidity and mortality in infant and mother.
Cesarean Section Delivery to Prevent Vertical Transmission of Human Immunodeficiency Virus Type 1 Associated Risks and Other Considerations
Authors: READ JENNIFER S.
Published: July 2010

Abstract: Delivery by elective cesarean section (ECS), cesarean section prior to labor and rupture of membranes, is associated with a lower rate of vertical transmission of HIV compared with other modes of delivery. The efficacy of ECS among women receiving combination antiretroviral therapy or among women with low viral loads is unknown. In assessing the possible utility of ECS as an intervention to decrease vertical transmission in the United States and other countries, the potential risks associated with operative delivery as well as other considerations should also be addressed. Although cesarean section delivery is associated with an increased rate of postpartum morbidity compared with vaginal delivery in the general population, operative delivery performed emergently carries a higher risk of complications than scheduled or elective procedures. Analyses of the risk of postpartum morbidity according to mode of delivery among HIV‐infected women have been performed in the Women and Infants Transmission Study (WITS), the largest database in North America with relevant data, as well as other, smaller databases. These analyses suggest a similar pattern to that observed in the general population. In addition to quantifying the incidence of postpartum morbidity events, it is also important to distinguish between minor and major morbidity. Neonatal morbidity related to ECS is generally due to iatrogenic preterm birth, that is, situations where the gestational age is not accurately assessed prior to delivery. Occupationally acquired HIV infection related to obstetric procedures is a possibility, although risk related to mode of delivery is unknown. The results of economic analyses of ECS compared to vaginal delivery in the US indicate that ECS is a cost‐effective intervention in preventing vertical transmission of HIV among women who refrain from breastfeeding. However, more precise estimates of the risk of vertical transmission among women receiving combination antiretroviral therapy and of the potential risks of maternal and pediatric adverse events related to receipt of such therapy are needed. In summary, the benefit of ECS must be weighed against potential risks, and issues such as cost‐effectiveness also should be taken into consideration.
Influence of Infant Feeding Patterns on Early Mother‐to‐Child Transmission of HIV‐1 in Durban, South Africa
Authors: COUTSOUDIS A.
Published: July 2010

Abstract: Previous studies on the effect of breastfeeding on mother‐to‐child transmission (MTCT) of HIV have not attempted to examine the influence of different types of breastfeeding practice. To attempt to address some of these inadequacies, infant feeding practices of 549 HIV‐infected women involved in a trial in Durban, South Africa were documented prospectively. Women were counseled on infant feeding choices according to UNAIDS guidelines, and those who chose to breastfeed were encouraged to practice exclusive breastfeeding. The MTCT rates of HIV‐1 at 3 months were compared in the three different feeding groups (never breastfed, exclusive breastfeeding, and mixed breast‐feeding). At 3 months, 18.8% of 156 never‐breastfed children were infected compared to 21.3% of 393 breastfed children (p= 0.50). Children exclusively breastfed to at least 3 months (n= 103) were less likely to be infected (14.3%) than those receiving mixed feeding before 3 months (24.1%) (p= 0.03). After adjustment for potential confounders (maternal CD4:CD8 ratio, syphilis screening test results, and preterm delivery), exclusive breastfeeding carried a significantly lower risk of HIV‐1 transmission than mixed feeding (hazard ratio [HR] 0.52, 95% CI: 0.28‐0.98) and an equivalent risk to no breastfeeding (HR 0.85, 95% CI: 0.51‐1.42). Our findings have important implications for HIV and infant feeding policies in developing countries, and it is critical that further research be undertaken. In the meantime, breastfeeding policies for HIV‐infected women require urgent review. If confirmed, exclusive breastfeeding may offer HIV‐infected women in developing countries an affordable, culturally acceptable, and effective means of reducing MTCT of HIV‐1 while maintaining the overwhelming benefits of breastfeeding.
Mastitis and Transmission of Human Immunodeficiency Virus through Breast Milk
Authors: SEMBA RICHARD D.
Published: July 2010

Abstract:Mastitis, an inflammation in the breast, has recently been linked with higher human immunodeficiency virus (HIV) load in breast milk and higher risk of mother‐to‐child transmission of HIV. Among 334 HIV‐infected women in Malawi who were breastfeeding, the prevalence of mastitis, as indicated by elevated breast milk sodium, was 16.4% at six weeks and 2.8% at six months postpartum. Mastitis is associated with significantly higher concentrations of immunological and inflammatory mediators in breast milk, including lactoferrin, lysozyme, secretory leukocyte protease inhibitor, interleukin‐8, and RANTES. Mastitis is potentially preventable by improving micronutrient status of breastfeeding women and can be treated with antibiotics and clinical management. These studies in Malawi suggest that mastitis may contribute to transmission of HIV through breast milk.