bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemokines and soluble adhesion molecules in renal transplant recipients with cytomegalovirus infection
Authors: Nordøy I , Müller F , Nordal K P , Rollag H , Aukrust P , Frøland S S 
Published: March 2003

SUMMARY
Cytomegalovirus (CMV) infection is associated with leucocyte infiltration in various organs, which supports a role for chemokines and adhesion molecules in the pathogenesis of CMV infection. In a prospectively conducted study of renal transplant recipients, 10 patients with CMV disease, five patients with asymptomatic CMV infection and 10 patients who did not have any CMV infection were included. During CMV infection, and in particular during CMV disease, plasma levels of the chemokines IL-8, macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1 (MCP-1) and the soluble adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and L-selectin increased and were positively correlated with the degree of CMV pp65 antigenaemia. Furthermore, a decrease in plasma levels of these chemokines and adhesion molecules was observed following ganciclovir therapy in the patients with CMV disease. This could suggest a role for these molecules in the pathogenesis of CMV infection.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) has opposing effects on the capacity of monocytesversusmonocyte-derived dendritic cells to stimulate the antigen-specific proliferation of a human T cell clone
Authors: Heystek H C , Mudde G C , Ohler R , Kalthoff F S 
Published: March 2003

SUMMARYGM-CSF is widely used in combination with IL-4 to differentiate monocytes into potent T cell stimulatory cells, referred to as monocyte-derived dendritic cells (MoDC). These cytokines further increased the stimulatory function of MoDC when present during their incubation with antigen, as determined by the proliferative response of an allergen-specific T cell clone. Conversely, the incubation of freshly isolated monocytes with antigen in the presence of GM-CSF or GM-CSF and IL-4 strongly inhibited the specific stimulation of the T cells, compared with monocytes pulsed in the absence of cytokines. This suppression was partly due to the secretion of prostaglandin E2 (PGE2) and IL-10 by GM-CSF-treated monocytes, since the combined use of indomethacin and anti-IL-10 antibodies during GM-CSF incubation and antigen pulsing restored T cell growth to about 65% of control levels. As confirmed by culture supernatant transfer experiments, maximal inhibition of T cell stimulation was also dependent on the direct contact between the T cells and GM-CSF-treated monocytes during antigen presentation. Collectively, these results imply that GM-CSF can either inhibit or enhance the re-stimulation of primed T cells by antigen-presenting monocytes or MoDC, respectively.
Polymorphisms in the IL-1 receptor antagonist gene VNTR are possible risk factors for juvenile idiopathic inflammatory myopathies
Authors: Rider L G , Artlett C M , Foster C B , Ahmed A , Neeman T , Chanock S J , Jimenez S A , Miller F W ,   FOR THE CHILDHOOD MYOSITIS HETEROGENEITY COLLABORATIVE STUDY GROUP
Published: March 2003

SUMMARY
Although HLA-DRB1 and -DQA1 alleles have been associated with adult and juvenile idiopathic inflammatory myopathies (JIIM), they only partially account for the genetic risk for these autoimmune disorders. Because IL-1α and IL-1β, and the anti-inflammatory competitive inhibitor, IL-1 receptor antagonist (IL-1Ra), have been implicated in the pathogenesis of myositis, we assessed the role of variable number tandem repeat (VNTR) polymorphisms of the IL-1Ra gene (IL-1RN) in the aetiology of JIIM: IL-1RN VNTR polymorphisms were performed on 250 JIIM patients and 471 race-matched controls and were correlated with clinical characteristics. The IL-1RN A1 allele, associated with increased proinflammatory activity, was found to be a risk factor for Caucasians with JIIM (96.0% carriage rate versus 90.2% in race-matched controls, Pcorr= 0.037, odds ratio (OR) = 2.5, confidence interval (CI) = 1.1–5.8), but not for African-Americans, in whom the A3 allele was a possible risk factor (7.0% versus 1.1% in race-matched controls, Pcorr= 0.07, OR = 6.5, CI = 1.1–40.3). IL-1RN genotypes did not correlate with circulating levels of IL-1Ra, which were higher in patients than in controls. The polymorphic IL-1RN locus could be the first non-MHC genetic risk factor identified for JIIM, and different alleles may confer susceptibility for different ethnic groups.
Pulmonary tuberculosis and serum IgE
Authors: Ohrui T , Zayasu K , Sato E , Matsui T , Sekizawa K , Sasaki H 
Published: March 2003

SUMMARYSeveral recent studies indicate that mycobacterium or viral infection may reduce IgE levels or suppress atopy or both. The present study was undertaken to investigate whether Mycobacterium tuberculosis infection and its successful treatment down-regulate serum total IgE levels, a marker of a Th2 response, due to enhancement of a Th1 response in adult patients with tuberculosis (TB). We prospectively studied the changes in serum total IgE and DTH response to tuberculin, a marker of a Th1 response in 10 healthy controls, 20 patients with pulmonary TB, and 19 asthma patients without TB. Measurement of serum total IgE and tuberculin skin tests were performed before initiation of treatment and after successful completion of 6 months treatment in TB patients, and at the corresponding intervals in controls and asthmatics. The initial serum total IgE concentrations were significantly higher in TB patients than in healthy controls (282 ± 26 U/ml (mean ±  s.e.m.) in TB patients versus 126 ± 56 U/ml in controls; P = 0.03). However, serum total IgE concentrations significantly decreased (282 ± 26 U/ml before versus 151 ± 12 U/ml after treatment; P = 0.03) and tuberculin indurations significantly increased (23.6 ± 1.8 mm before versus 29.6 ± 2.1 mm after treatment; P = 0.04) in TB patients. In contrast, initial serum IgE concentrations and tuberculin indurations did not differ significantly from post-observation data in both healthy controls and asthmatics (P &gt; 0.30). The present study confirmed that immune responses to M. tuberculosis down-regulate a Th2 immune response, and might contribute to the decreased prevalence of allergic disorders.
Anti-topoisomerase II α autoantibodies in systemic sclerosis—association with pulmonary hypertension and HLA-B35
Authors: Grigolo B , Mazzetti I , Meliconi R , Bazzi S , Scorza R , Candela M , Gabrielli A , Facchini A 
Published: March 2003

SUMMARY
We have previously detected autoantibodies against topoisomerase II α (anti-topo II α) in sera from patients with idiopathic pulmonary fibrosis. To determine whether anti-topo II α is also present in systemic sclerosis (SSc) patients with pulmonary involvement, we screened sera from 92 patients and 34 healthy controls. Presence of anti-topo II α was investigated with respect to clinical and serological features, including the frequencies of HLA class I and II alleles. Anti-topo II α was detected in 20/92 (21.7%) patients. No association was found with either anti-topoisomerase I (Scl-70 or anti-topo I) or anti-centromere antibodies. However, anti-topo II α was associated with the presence of pulmonary hypertension (PHT) (as opposed to pulmonary fibrosis), and with a decrease of carbon monoxide diffusing capacity. Anti-topo II α was strongly associated with the presence of the class I antigen HLA-B35. No significant association was found with HLA class II antigens. HLA-B35 also turned out to be associated with the presence of PHT. These results indicate that in SSc patients, the presence of anti-topo II α is associated with PHT, and that the simultaneous presence of HLA-B35 seems to add to the risk of developing PHT.
Both Th1- and Th2-derived cytokines in serum are elevated in Graves' ophthalmopathy
Authors: Wakelkamp I M M J , Gerding M N , Van Der Meer J W C , Prummel M F , Wiersinga W M 
Published: March 2003

SUMMARY
Increased serum cytokine levels have been reported in patients with autoimmune thyroid disease, but less is known about their levels in patients with Graves' ophthalmopathy (GO). It is not known whether GO is a cell-mediated or humoral autoimmune disease. We investigated whether serum cytokines are elevated in GO patients and whether the cytokines were Th1- or Th2-derived. In addition, elevated cytokines might reflect the activity of GO, and thus we investigated whether cytokine levels could predict the clinical response to orbital radiotherapy. We studied 62 consecutive patients with moderately severe untreated GO and 62 healthy controls, matched for sex, age and smoking habits. Serum concentrations of IL-1RA, sIL-2R, IL-6, sIL-6R, tumour necrosis factor-alpha (TNF-α) RI and II and sCD30 were measured using highly sensitive ELISAs, in the patients before and 3 and 6 months after radiotherapy. All patients were euthyroid, with anti-thyroid drugs, before and during the entire study period. All baseline cytokine and cytokine receptor levels were significantly elevated in GO patients compared with healthy controls, except for IL-1RA. The levels did not correlate with parameters of the thyroid disease, nor with the duration, activity or severity of GO. However, backward logistic regression analysis showed that IL-6, sCD30 and TNFαRI were able to predict a beneficial response to orbital radiotherapy. We therefore conclude that both Th1- and Th2-derived cytokines are elevated in GO patients compared with its controls. IL-6, sCD30 and TNFαRI had some value for predicting therapeutic outcome to orbital irradiation, and may thus reflect active eye disease.
Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation
Authors: Rocksén D , Lilliehöök B , Larsson R , Johansson T , Bucht A 
Published: March 2003

SUMMARYInhalation of bacterial endotoxin induces an acute inflammation in the lower respiratory tract. In this study, the anti-inflammatory effects of the anti-oxidant N-acetylcysteine (NAC) and the glucocorticoid dexamethasone were investigated in mice exposed to aerosolized endotoxin (lipopolysaccharide (LPS)). Powerful reduction of neutrophils in bronchoalveolar lavage fluid (BALF) was obtained by a single i.p. injection of dexamethasone (10 mg/kg), whereas treatment with NAC only resulted in reduction of neutrophils when administered at a high dose (500 mg/kg). Measurement of cytokine and chemokine expression in lung tissue revealed a significant decrease of tumour necrosis factor-alpha, IL-1α, IL-1β, IL-6, IL-12p40, and MIP-1α mRNA when mice where treated with dexamethasone but not when treated with NAC. Analysis of oxidative burst demonstrated a remarkable reduction of oxygen radicals in BALF neutrophils after treatment with dexamethasone, whereas the effect of NAC was not significantly different from that in untreated animals. In conclusion, dexamethasone exerted both anti-inflammatory and anti-oxidative effects in acute airway inflammation, probably by blocking early events in the inflammatory cascade. In contrast, treatment with NAC resulted in a weak reduction of the inflammatory response but no inhibition of proinflammatory cytokines or reduction of oxidative burst in neutrophils. These results demonstrate dramatic differences in efficiency and also indicate that the two drugs have different actions. Combined treatment with NAC and dexamethasone revealed an additive action but no synergy was observed.
CXC chemokines Groα/IL-8 and IP-10/MIG inHelicobacter pylorigastritis
Authors: Eck M , Schmausser B , Scheller K , Toksoy A , Kraus M , Menzel T , Müller-Hermelink H K , Gillitzer R 
Published: March 2003

SUMMARYInfection with Helicobacter pylori causes chronic active gastritis, which is characterized by neutrophils infiltrating the gastric epithelial layer and the underlying lamina propria as well as by T, B lymphocytes and macrophages accumulating in the lamina propria. In this study, the chemokine profile responsible for the recruitment of these inflammatory cells is investigated. Using both RNA/RNA in situ hybridization and immunohistochemistry, the expression of the neutrophil and/or lymphocyte-attractant CXC chemokines growth-related oncogene alpha (Groα), IL-8, interferon-gamma (IFN-γ)-inducible protein-10 (IP-10), monokine induced by IFN-γ (MIG) and the CC chemokines macrophage inflammatory protein-1α (MIP-1α), -1β, regulated on activation normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1) is studied and microanatomically localized in the gastric mucosa. Macrophages in the lamina propria at sites with neutrophil infiltration and gastric epithelium infiltrated by neutrophils highly expressed the neutrophil-attractant chemokines Groα and IL-8. Additionally, Groα and IL-8 were expressed by neutrophils themselves localized within gastric epithelium, in the foveolar lumen and in the cellular debris overlying mucosal erosion. IP-10 and to a lower extent MIG, both selectively chemotactic for inflammatory T cells, were expressed by endothelial cells of gastric mucosal vessels and by mononuclear cells at sites with T cell infiltration. Expression of all other CC chemokines tested was significantly lower. These in vivo data indicate that a set of predominantly CXC chemokines modulates the inflammation in H. pylori gastritis. Groα and IL-8 may play an important role in neutrophil trafficking from the mucosal vessel into the gastric epithelium, whereas IP-10 and MIG contribute to the recruitment of inflammatory T cells into the mucosa.
Decreased expression levels of L-selectin on subsets of leucocytes and increased serum L-selectin in severe psoriasis
Authors: Inaoki M , Sato S , Shimada Y , Kawara S , Steeber D A , Tedder T F 
Published: March 2003

SUMMARYL-selectin is a leucocyte adhesion molecule involved in leucocyte interactions with vascular endothelial cells. Following leucocyte activation L-selectin is endoproteolytically released from the cell surface. To assess whether psoriasis vulgaris results in systemic leucocyte activation, we examined expression levels of L-selectin on subsets of peripheral blood leucocytes from patients with psoriasis (n = 25) and normal control subjects. Serum levels of soluble L-selectin were quantified by ELISA in patients with psoriasis (n = 75), pustulosis palmaris et plantaris, and contact dermatitis, as well as normal control subjects. Psoriasis severity was evaluated by psoriasis area and severity index (PASI). L-selectin expression levels on CD4+ T cells, B cells, monocytes, and neutrophils from patients with severe-type psoriasis (PASI ≥ 15) was significantly decreased compared with leucocytes from normal control subjects. Furthermore, L-selectin expression on CD4+ T cells showed good inverse correlation with PASI scores. Monocyte L-selectin expression was restored when the skin lesions of psoriasis were remitted. The frequencies of L-selectin+ CD4+ T cells or L-selectin+ CD8+ T cells from patients with psoriasis were almost normal. Serum L-selectin levels in patients with severe-type psoriasis were significantly higher than those in normal control subjects. These results suggest that subsets of leucocytes may be activated in psoriasis, and that L-selectin expression levels on some leucocyte subsets, especially CD4+ T cells, tend to correlate with disease severity of psoriasis.
Gram-negative bacteria induce proinflammatory cytokine production by monocytes in the absence of lipopolysaccharide (LPS)
Authors: Uronen H , Williams A J , Dixon G , Andersen S R , Van Der Ley P , Van Deuren M , Callard R E , Klein N 
Published: March 2003

SUMMARY
Tumour necrosis factor-alpha (TNF-α), IL-1α and IL-6 production by human monocytes in response to a clinical strain of the Gram-negative encapsulated bacteria Neisseria meningitidis and an isogenic lpxA− strain deficient in LPS was investigated. Wild-type N. meningitidis at concentrations between 105 and 108 organisms/ml and purified LPS induced proinflammatory cytokine production. High levels of these cytokines were also produced in response to the lpxA− strain at 107 and 108 organisms/ml. The specific LPS antagonist bactericidal/permeability-increasing protein (rBPI21) inhibited cytokine production induced by LPS and wild-type bacteria at 105 organisms/ml but not at higher concentrations, and not by LPS-deficient bacteria at any concentration. These data show that proinflammatory cytokine production by monocytes in response to N. meningitidis does not require the presence of LPS. Therapeutic strategies designed to block LPS alone may not therefore be sufficient for interrupting the inflammatory response in severe meningococcal disease.
Anti-neutrophil cytoplasmic antibodies (ANCA) from patients with systemic vasculitis recognize restricted epitopes of proteinase 3 involving the catalytic site
Authors: Griffith M E , Coulthart A , Pemberton S , George A J T , Pusey C D 
Published: March 2003

SUMMARYANCA with specificity for proteinase 3 (PR3), a neutrophil primary granule enzyme, are of diagnostic value in Wegener's granulomatosis (WG) and certain other forms of systemic vasculitis. There is evidence to suggest that they play a pathogenic role in disease, and that the interaction of ANCA with PR3 is likely to be important. We showed, using a resonant mirror biosensor, that C-ANCA from different patients recognized the same or closely related epitopes on PR3. Studies using linear peptides in the SPOT system confirmed the highly restricted nature of this interaction and identified five linear epitopes. Fluid-phase inhibition studies, using a different set of peptides, validated the sequences involved. Using a computer-generated model of the structure of PR3, four of five epitopes were shown to be intimately linked with the catalytic site. The restricted number of epitopes, and their location at the catalytic site, has important implications for the role of C-ANCA in the pathogenesis of vasculitis.
Accelerated calcium influx and hyperactivation of neutrophils in chronic granulomatous disease
Authors: Tintinger G R , Theron A J , Steel H C , Anderson R 
Published: March 2003

SUMMARYThe relationship between activation of NADPH-oxidase, alterations in membrane potential and triggering of Ca2+ fluxes in human phagocytes has been investigated using neutrophils from four subjects with chronic granulomatous disease (CGD). Cytosolic Ca2+ and membrane potential were measured by spectrofluorimetry, and net efflux and influx of Ca2+ by radiometric procedures. Exposure of normal neutrophils to the chemotactic tripeptide, N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP; 1 μm) was accompanied by an abrupt increase in cytosolic Ca2+ coincident with membrane depolarization and efflux of the cation. These events terminated at around 30 s after the addition of FMLP and were followed by membrane repolarization and store-operated influx of Ca2+, both of which were superimposable and complete after about 5 min. Activation of CGD neutrophils was also accompanied by an increase in cytosolic Ca2+, which, in spite of an efficient efflux response, was prolonged in relation to that observed in normal cells. This prolonged increase in cytosolic Ca2+ in activated CGD neutrophils occurred in the setting of trivial membrane depolarization and accelerated influx of Ca2+, and was associated with hyperactivity of the cells according to excessive release of elastase and increased activity of phospholipase A2. Treatment of CGD neutrophils with the type 4 phosphodiesterase inhibitor, rolipram (1 μm) restored Ca2+ homeostasis and attenuated the increase in elastase release. These findings support the involvement of NADPH-oxidase in regulating membrane potential and Ca2+ influx in activated neutrophils, and may explain the disordered inflammatory responses and granuloma formation which are characteristic of CGD.
The IL-8 release from cultured human keratinocytes, mediated by antibodies to bullous pemphigoid autoantigen 180, is inhibited by dapsone
Authors: Schmidt E , Reimer S , Kruse N , Bröcker E-B , Zillikens D 
Published: March 2003

SUMMARYBullous pemphigoid (BP) is a subepidermal blistering disease associated with autoantibodies to the hemidesmosomal 180 kD BP autoantigen (BP180). However, the binding of autoantibodies to BP180 alone is not sufficient for blister formation in this disease and the infiltration of neutrophils into the skin is required. Dapsone and nicotinamide inhibit neutrophil chemotaxis and are used effectively in treating BP. IL-8 is a known chemoattractant for neutrophils and has been implicated in the inflammatory process of both human and experimental murine BP. We have recently shown that antibodies to BP180 mediate a dose and time-dependent release of IL-6 and IL-8 from cultured normal human epidermal keratinocytes (NHEK). In the present study, we addressed the question whether dapsone or nicotinamide influence this cytokine release. We demonstrate that dapsone, but not nicotinamide, in its pharmacological range, inhibits the IL-8, but not the IL-6 release from NHEK, induced by anti-BP180 IgG, in a dose-dependent fashion as detected by ELISA. IL-8 mRNA levels, as determined by RT-PCR, were the same in cells treated with BP IgG alone compared to cells treated with BP IgG plus dapsone. This observation suggests that dapsone inhibits the BP IgG-induced IL-8 release from cultured NHEK by mechanisms at the post-transcriptional level. Our findings contribute to the understanding how dapsone leads to a reduced influx of neutrophils into BP lesions and, finally, to the cessation of blister formation in this disease.
Differential responses of CD45+ve T-cell subsets to MBP in multiple sclerosis
Authors: Ponsford M , Mazza G , Coad J , Campbell M J , Zajicek J , Wraith D C 
Published: March 2003

SUMMARYThe proliferative response of preparations of whole PBMC populations from 20 healthy individuals and 28 multiple sclerosis (MS) patients to purified protein derivative (PPD) and myelin basic protein (MBP) was monitored in a kinetic assay over a period of up to 10 days. PPD produced a classical secondary response in both groups, the magnitude being significantly reduced in the MS cohort. The magnitude and pattern of response to MBP did not differ between the two populations. The kinetic profile characteristic of a primary response was observed in both groups. Enrichment of the CD45RO+ve and CD45RA+ve T-cell subsets in PBMC led to a secondary response to PPD in the RO+ve and primary response in the RA+ve population in both groups. The response to MBP in both RO+ve and RA+ve populations exhibited primary kinetics in both MS patients and healthy individuals. However, the use of T-cell subset enriched populations allowed a finer dissection of the response to MBP which highlighted the more active role of RO-positive cells in MS patients. The most striking difference between patients and healthy individuals occurred on day 4 of culture when a greater response to MBP occurred in the CD45RO enriched population, paralleling the response to PPD, in the majority of patients. Futhermore in 4/8 patients and only1/8 healthy individuals the response in the RO+ve cultures was maintained at a higher level than that seen in the corresponding RA+ve cultures throughout the culture period. This data indicates that a measurable memory response to MBP exists in MS patients implying prior activation of MBP reactive T lymphocytes during the course of disease.