Newsgroup: it.scienza.medicina
Titolo: Sclerosi multipla

Sono Lisa ho 22 anni e circa due anni fa ho avuto un problema di
deambulazione alla gamba sinistra che il mio medico curante risolse con un
plantare, a giugno di questo anno pero' il problema si č ripresentato in
maniera piu grave di fatti interessava oltre che la gamba sinistra anche il
braccio ( perdita di forza e difficolta nell'alzarlo) a quel punto fui
ricoverata e mi sottoposero ad una R.M.
Il risultato lo potete immaginare avevo due placche nell'encefalo destro del
cervello, e essendo un tipetto sveglio chiesi  al neurologo se avevo la
sclerosi, da quel giorno essendo una ignorante in materia sono andata
navignado in rete trovando una marea di informazioni e alle mille domande
che vorrei fare c'č una che preferirei porre a chi puo darmi aiuto.
Ho visto che nei 9 mesi di gravidanza l'effetto delle ricadute non c'č
quindi io chiedo se  c'č nel mondo uno studio per verificare il perche di
tale fenomeno? e sarebbe possibile creare nell'essere umano le stesse
condizioni che ci sono quando una donna č incinta e mantenerla simulando
tutti i processi biologici dell'evento in maniera latente?......perche
simulando questo evento non ci sarebbero piu ricadute.
Forse ho fatto una domanda stupida ma vorrei chiarimenti al
riguardo...ringrazio anticipatamente chi vuole aiutarmi e faccio un invito a
tutti quelli che hanno il mio problema a scrivere per confrontare le nostre
esperienze anche sulle eventuali terapie
P.S.
a febbraio devo fare un altra risonanza per vedere se č il caso di iniziare
con l'interferone( altro dilemma ....di fatti non tutti sono dello stesso
parere) credo che per questa malattia ci sia molta confusione e correnti di
pensiero diverse!!!

 quindi io chiedo ........
<cut>
Non posso darti consigli seri, perchè non sono un neurologo. Ma vorrei
chiederti: perchè sostieni che la gravidanza abbia evitato le "ricadute"?
Nella storia della sclerosi multipla sono normanlmente presenti dei periodi
di remissione spontanea, più o meno lunghi, a volte anche definitivi. La sua
evoluzione credo non sia tanto prevedibile.
Comunque attendo anch'io la risposta di qualche esperto alla tua
interessante questione.
Ti auguro ogni fortuna,
 Saluti,
 The Dentist

Ma vorrei chiederti: perchè sostieni che la gravidanza abbia evitato le
"ricadute"?.....
Sò di per certo che durante i 9 mesi di gravidanza statisticamente mai
nessuna ha avuto ricadute , con un alta percentuale di averla nei mesi
successivi.Per questo motivo pensavo che in quei nove mesi accada qualche
avvenimento ormonale a me sconosciuto che a quanto pare possa placare la
malattia.......in poche parole chiedevo una opinione su questo punto.
Volevo sapere se c'erano studi in atto per determinare i fattori che in quei
9 mesi difendono l'ammalato da nuove ricadute.

ricoverata e mi sottoposero ad una R.M.
 
Qui c'e' una mailing list in proposito:
http://www.geocities.com/Heartland/Valley/7622/presents.htm
ciao
Lisa (un'altra)

chiederti: perchè sostieni che la gravidanza abbia evitato le "ricadute"?
E' proprio vero... Ho letto (non mi ricordo dove) che nel nel 3° trimestre il
rischio di ricaduta-SM è del 70-72% (non ricordo esattamente) inferiore a
quello della popolazione normale. Motivo? Boooooohhhh !!!
(Vedi risposta a Lisa per i dettagli)
Bye, Alessio
NB Non sono un medico!

pensiero diverse!!!
In effetti è così. La SM, per molti versi, è un autentico "rompicapo" e le
varie terapie non danno sempre i medesimi risultati. Io sono
un "interferoniano" e, anche all'ultimo meeting della American Neurological
Association, i 'neuro' che sono intervenuti hanno ribadito che l'utilizzo
"precoce" degli "ABC drugs" (Avonex, Betaferon e Copaxone + Rebif) consente di
avere i risultati migliori.
Ancora in bocca al lupo!


 9 mesi difendono l'ammalato da nuove ricadute.
L'argomento è ancora un po' complicato da discutere; comunque
questi qua sono alcuni abstract di pubblicazioni recenti
sull'argomento (il messaggio è molto lungo; magari se i
moderatori aggiungono [Lungo] al titolo è meglio; in ogni caso
scusate per la prolissità):
J Clin Endocrinol Metab 2001 Oct;86(10):4933-8
IL-12, TNF-alpha, and hormonal changes during late pregnancy and
early postpartum: implications for autoimmune disease activity
during these times.
Elenkov IJ, Wilder RL, Bakalov VK, Link AA, Dimitrov MA, Fisher
S, Crane M, Kanik KS, Chrousos GP.
Arthritis and Rheumatism Branch, National Institute of Arthritis
and Musculoskeletal and Skin Diseases, National Institutes of
Health, Bethesda, MD 20892, USA.
Clinical observations indicate that some autoimmune diseases,
such as rheumatoid arthritis and multiple sclerosis, frequently
remit during pregnancy but exacerbate, or have their onset, in
the postpartum period. The immune basis for these phenomena is
poorly understood. Recently, excessive production of IL-12 and
TNF-alpha was causally linked to rheumatoid arthritis and
multiple sclerosis. We studied 18 women with normal pregnancies
in their third trimester and during the early postpartum period.
We report that during the third trimester pregnancy, ex vivo
monocytic IL-12 production was about 3-fold and TNF-alpha
production was approximately 40% lower than postpartum values. At
the same time, urinary cortisol and norepinephrine excretion and
serum levels of 1,25-dihydroxyvitamin were 2- to 3-fold higher
than postpartum values. As shown previously, these hormones can
directly suppress IL-12 and TNF-alpha production by
monocytes/macrophages in vitro. We suggest that a cortisol-,
norepinephrine-, and 1,25-dihydroxyvitamin-induced inhibition and
subsequent rebound of IL-12 and TNF-alpha production may
represent a major mechanism by which pregnancy and postpartum
alter the course of or susceptibility to various autoimmune
disorders.
PMID: 11600565 [PubMed - indexed for MEDLINE]
Neurol Sci 2000;21(4 Suppl 2):S857-60
The prognostic value of age, gender, pregnancy and endocrine
factors in multiple sclerosis.
Zaffaroni M, Ghezzi A.
Multiple Sclerosis Center, Gallarate Hospital, University of
Milan, VA, Italy.
The evolution of multiple sclerosis at the time of diagnosis
remains unpredictable since a reliable prognostic marker is not
yet available. Nevertheless, a series of useful prognostic
indicators have been singled out from epidemiological studies.
Young age at onset, female gender, relapsing/remitting course,
and sensitive or visual disturbances as initial symptoms are
considered favourable prognostic factors. Conversely, late age at
onset, male gender, progressive course, and pyramidal or
cerebellar symptoms at the first episode predict an unfavourable
evolution. Another prognostic indicator has been recognized in
pregnancy: although the overall effect of pregnancy on short-term
MS course is neutral, in the long-term it seems to protect from
disease progression. Most prognostic indicators seem to act
through the neuro-endocrine-immune network, modulating the immune
response in the context of the Th1/Th2 paradigm.
Publication Types:
Review
Review, Tutorial
PMID: 11205363 [PubMed - indexed for MEDLINE]
Mult Scler 2000 Oct;6 Suppl 2:S18-20; discussion S33
High dose IVIG in the post partum period for prevention of
exacerbations in MS.
Haas J.
Department of Neurology, Judisches Krankenhaus Berlin, Abteilung
fur Neurologie, Germany.
The influence of pregnancy on the course of autoimmune diseases
is well documented. In multiple sclerosis the European PRIMS
study confirmed an ameliorating effect during pregnancy but on
increase of exacerbations after delivery. The efficacy of IVIG in
autoimmune mediated diseases has been frequently reported. Based
on the experiences of Achiron we recommend IVIG to prevent
exacerbations after delivery. Since 1995 we recommend 60 g IVIG
within 3 days after delivery and 10 g monthly in patients
estimated to be on high risk for exacerbation. The data were
compared to the PRIMS study. The baseline data were comparable,
but the exacerbation rate after delivery in our observation was
33% lower than expected. The lowest risk for an exacerbation
within the first 3 months after delivery we observed in women
treated with long-term IVIG monthly. Until now the overall
tolerance was excellent The results with IVIG after delivery
suggest that immunoglobulins may be a promising therapeutical
approach not only in MS but also in other autoimmune mediated
diseases with a risk of exacerbation after delivery. A European
wide study with IVIG after delivery in MS is in preparation to
confirm our preliminary data.
PMID: 11188773 [PubMed - indexed for MEDLINE]
J Neurol Sci 2000 Dec 15;182(1):5-15
Early pregnancy factor suppresses experimental autoimmune
encephalomyelitis induced in Lewis rats with myelin basic protein
and in SJL/J mice with myelin proteolipid protein peptide
139-151.
Zhang B, Harness J, Somodevilla-Torres MJ, Hillyard NC, Mould AW,
Alewood D, Love SG, Alewood PF, Greer JM, Cavanagh AC, McCombe
PA, Morton H.
Department of Surgery, The University of Queensland, Royal
Brisbane Hospital, 4029, Queensland, Australia.
Early pregnancy factor (EPF) is a secreted protein with
immunosuppressive and growth factor properties. During pregnancy,
it appears in maternal serum within 6-24 h of fertilization, is
present for at least the first two-thirds of pregnancy in all
species studied and is essential for embryonic survival. It is a
homologue of chaperonin 10, a heat shock protein, but, unlike
other members of this family, EPF has an extracellular role. As
it has the ability to modulate CD4+ T cell-dependent immune
responses, its role in treatment of experimental autoimmune
encephalomyelitis (EAE) was investigated. EAE is a CD4+ T
cell-mediated disease, the best available animal model of
multiple sclerosis (MS). Two models of EAE were investigated,
acute EAE induced in Lewis rats by inoculation with myelin basic
protein (MBP-EAE) and chronic relapsing EAE induced in SJL/J mice
by inoculation with myelin proteolipid protein peptide (residues
139-151) (PLP-EAE). EPF, delivered intraperitoneally or orally to
rats or intraperitoneally to mice, suppressed clinical signs of
disease. Mice with PLP-EAE were also treated with
interferon-beta, with and without EPF. Both EPF and IFN-beta
suppressed clinical signs of EAE and, when administered together,
gave greater suppression than when given separately. These
findings suggest that EPF may be a potential candidate for use in
treatment of MS and may be of use in combined therapy with
IFN-beta.
PMID: 11102634 [PubMed - indexed for MEDLINE]
J Neuroimmunol 2000 Nov 1;111(1-2):77-85
Female sex steroids: effects upon microglial cell activation.
Drew PD, Chavis JA.
University of Arkansas for Medical Sciences, Department of
Anatomy, Slot 510, Shorey Bldg., Rm. 922, 4301 W. Markham St.,
72205, Little Rock, AR, USA.
Multiple sclerosis occurs more commonly in females than males.
However, the mechanisms resulting in gender differences in
multiple sclerosis are unknown. Activated microglia are believed
to contribute to multiple sclerosis pathology, perhaps in part
due to production of nitric oxide (NO) and TNF-alpha, molecules
which can be toxic to cells including oligodendrocytes. The
current study demonstrates that the female sex steroids estriol,
beta-estradiol and progesterone inhibit lipopolysaccharide (LPS)
induction of nitric oxide (NO) production by primary rat
microglia and by the mouse N9 microglial cell line. These
hormones act by inhibiting the production of inducible nitric
oxide synthase (iNOS) which catalyses the synthesis of NO.
Estriol likely inhibits iNOS gene expression since the hormone
blocks LPS induction of iNOS RNA levels. The pro-inflammatory
cytokines IFN-gamma and TNF-alpha are believed to be important
modulators of multiple sclerosis. Here, we demonstrate that
estrogens and progesterone also inhibit NO production by
microglial cells activated in response to these cytokines.
Activated microglia elicit TNF-alpha in addition to NO and we
further demonstrate that estrogens and progesterone repress
TNF-alpha production by these cells. Finally, estriol and
progesterone, at concentrations consistent with late pregnancy,
inhibit NO and TNF-alpha production by activated microglia,
suggesting that hormone inhibition of microglial cell activation
may contribute to the decreased severity of multiple sclerosis
symptoms commonly associated with pregnancy.
PMID: 11063824 [PubMed - indexed for MEDLINE]
Neurology 2000 Sep 26;55(6):848-54
Oral contraceptives and the incidence of multiple sclerosis.
Hernan MA, Hohol MJ, Olek MJ, Spiegelman D, Ascherio A.
Departments of Epidemiology, Harvard School of Public Health,
Boston, MA 02115, USA.
BACKGROUND: Experimental and clinical data suggest a protective
effect of estrogens on the development and progression of MS.
METHODS: We assessed whether MS incidence was associated with
oral contraceptive use or parity in two cohort studies of U.S.
women, the Nurses' Health Study (NHS; 121,700 women aged 30 to 55
years at baseline in 1976) and the Nurses' Health Study II (NHS
II; 116,671 women aged 25 to 42 years at baseline in 1989).
Participants with a diagnosis of MS before baseline were
excluded. Oral contraceptive history and parity were assessed at
baseline and updated biennially. During follow-ups of 18 years
(NHS) and 8 years (NHS II) we documented a total of 315 definite
or probable cases of MS. RESULTS: Neither use of oral
contraceptives nor parity were significantly associated with the
risk of MS. As compared with women who never used oral
contraceptives, the age-adjusted relative risk (95% CI) was 1.2
(0.9, 1.5) for past users, and 1.0 (0.6, 1.7) for current users.
Similar results were obtained after adjustment for latitude,
ancestry, and other potential confounding factors. There was no
clear trend of MS risk with either increasing duration of use or
time elapsed since last use. Age at first birth was also not
associated with the risk of MS. CONCLUSIONS: These prospective
results do not support a lasting protective effect of oral
contraceptive use or pregnancy on the risk of MS. The decision to
use hormonal contraception should not be affected by its effects
on the risk of MS.
PMID: 10994007 [PubMed - indexed for MEDLINE]
J Interferon Cytokine Res 1999 Jun;19(6):631-6
Expression, purification, and characterization of interferon-tau
produced in Pichia pastoris grown in a minimal medium.
Johnson TM, Holaday SK, Sun Y, Subramaniam PS, Johnson HM,
Krishna NR.
Department of Biochemistry and Molecular Genetics, University of
Alabama at Birmingham, 35294, USA.
Interferon-tau (IFN-tau) is a novel type I IFN that was
originally identified as a pregnancy recognition hormone. IFN-tau
shares all of the biological properties of other type I IFNs
including antiviral activity and antiproliferative activity
through induction of the cell cycle inhibitor gene product
p21WAF1. It is a promising therapy for cancers, viral infections,
and for autoimmune disorders such as multiple sclerosis, without
the adverse side effects associated with IFN-alpha and IFN-beta.
Here, we describe novel growth and induction conditions for the
expression of functionally active and uniformly 15N-labeled
IFN-tau from Pichia pastoris in a minimal media for use in
initial 2D- and 3D-NMR studies in solution. Purified 15N-IFN-tau
was homogenous, as determined by sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE) and MALDI-TOF mass
spectrometer (MS), and retained full biological activity. MS
analysis confirmed uniform isotopic labeling of IFN-tau with 15N
incorporation exceeding 99%. Circular dichroism (CD) as well as
1D-NMR and 15N-1H heteronuclear single quantum coherence (HSQC)
spectra confirmed that purified 15N-labeled IFN-tau has a stable
secondary structure. Besides providing a route for isotope
labeling of IFN-tau, our procedure may be useful for the
expression and purification of other proteins that are difficult
to obtain in Pichia pastoris grown in minimal media.
PMID: 10433364 [PubMed - indexed for MEDLINE]
Neurology 1999 Apr 12;52(6):1230-8
Estriol ameliorates autoimmune demyelinating disease:
implications for multiple sclerosis.
Kim S, Liva SM, Dalal MA, Verity MA, Voskuhl RR.
Department of Neurology, University of California Los Angeles
School of Medicine, USA.
OBJECTIVE: To evaluate the use of estriol in the treatment of
experimental autoimmune encephalomyelitis (EAE) and other cell
mediated autoimmune diseases. BACKGROUND: Experimental autoimmune
encephalomyelitis is a T helper 1 (Th1)-mediated autoimmune
demyelinating disease that is a useful model for the study of
immune responses in MS. Interestingly, both EAE and MS have been
shown to be ameliorated during late pregnancy. METHODS: Estriol,
progesterone, and placebo pellets were implanted in mice during
the effector phase of adoptive EAE. Disease scores were compared
between treatment groups, and autoantigen-specific humoral and
cellular responses were examined. RESULTS: Estriol treatment
reduced the severity of EAE significantly compared with placebo
treatment whereas progesterone treatment had no effect. Estriol
doses that induced serum estriol levels that approximated estriol
levels during late pregnancy were capable of ameliorating
disease. Estriol-treated EAE mice had significantly higher levels
of serum antibodies of the immunoglobulin (Ig) G1 isotype
specific for the autoantigen myelin basic protein (MBP). Further,
MBP-specific T-lymphocyte responses from estriol-treated EAE mice
were characterized by significantly increased production of the
Th2 cytokine interleukin 10 (IL-10). T lymphocytes were shown to
be the primary source of IL-10 within antigen-stimulated
splenocyte populations. CONCLUSIONS: Estriol as a hormone
involved in immune changes during pregnancy may provide a basis
for the novel therapeutic use of estriol for MS and other
putative Th1-mediated autoimmune diseases that improve during
late pregnancy.
PMID: 10214749 [PubMed - indexed for MEDLINE]
Eur J Obstet Gynecol Reprod Biol 1999 Feb;82(2):191-4
Pregnancy and multiple sclerosis: a 2-year experience.
Orvieto R, Achiron R, Rotstein Z, Noy S, Bar-Hava I, Achiron A.
Department of Obstetrics and Gynecology, Rabin Medical Center,
Petah Tiqva, Israel.
OBJECTIVE: To present our experience with management of
parturients with multiple sclerosis and to examine the role of
intravenous immunoglobulin (IVIg) in the prevention of postpartum
exacerbations of the disease. METHODS: Fifteen patients with
multiple sclerosis with a relapsing-remitting course were
followed during pregnancy and 6 months postpartum. To prevent
postpartum exacerbations, 14 of the patients had received IVIg
after delivery. RESULTS: None of the patients who received
postpartum IVIg relapsed during the 6 months after delivery. None
of the observed obstetric complications nor the operative
deliveries could be related to the coexistence of multiple
sclerosis. CONCLUSION: Postpartum IVIg treatment is beneficial in
preventing acute childbirth-associated exacerbations in patients
with relapsing-remitting multiple sclerosis. Furthermore, this
disease does not seem to increase obstetric complications.
PMID: 10206414 [PubMed - indexed for MEDLINE]
Immunol Cell Biol 1998 Dec;76(6):483-96
Early pregnancy factor: an extracellular chaperonin 10 homologue.
Morton H.
University of Queensland, Department of Surgery, Clinical
Sciences Building, Royal Brisbane Hospital, Brisbane, Queensland,
Australia.
Early pregnancy factor (EPF) has been identified as a homologue
of chaperonin 10 (cpn10) with immunosuppressive and growth factor
properties. As a homologue of cpn10, it belongs to the heat shock
family of proteins (hsp) but, unlike other members of this
family, EPF is detected extracellularly. Early pregnancy factor
was first discovered in pregnancy serum by the rosette inhibition
test, and the novelty of its discovery was that its presence
could diagnose pregnancy within 6-24 h of a fertile mating. As
well as being a monitor of the presence of a viable embryo, it is
necessary for embryonic survival. In this capacity it acts as
both an immunosuppressant and growth factor. Early pregnancy
factor is also a product of proliferating primary and neoplastic
cells and functions as an autocrine growth factor both in vivo
and in vitro. It has a modifying effect on the outcome of
experimental autoimmune encephalomyelitis, an animal model of
multiple sclerosis. Early pregnancy factor is considered to be
one of the major factors involved in the modification of multiple
sclerosis observed during pregnancy.
Publication Types:
Review
Review, Tutorial
PMID: 9893026 [PubMed - indexed for MEDLINE]
Biochimie 1998 Aug-Sep;80(8-9):755-77
IFN-tau: a novel subtype I IFN1. Structural characteristics,
non-ubiquitous expression, structure-function relationships, a
pregnancy hormonal embryonic signal and cross-species therapeutic
potentialities.
Martal JL, Chene NM, Huynh LP, L'Haridon RM, Reinaud PB,
Guillomot MW, Charlier MA, Charpigny SY.
Inra, Station de Physiologie animale, Unite Endocrinologie de
l'Embryon, Jouy-en-Josas, France.
IFN-tau (IFN-tau) constitutes a new class of type I IFN which is
not virus-inducible, unlike IFN-alpha and IFN-beta, but is
constitutively produced by the trophectoderm of the ruminant
conceptus during a very short period in early pregnancy. It plays
a pivotal role in the mechanisms of maternal recognition of
pregnancy in ruminants and it displays high antiviral and
antiproliferative activities across species with a prominent lack
of cytotoxicity at high concentrations in vitro in cell culture
and possibly in vivo. It exhibits high antiretroviral activity
against HIV and exhibits immunosuppressive activity in a multiple
sclerosis model and reduces embryo and fetal mortality by
stimulation of IL-10 production. In this review all the
biochemical and para-hormonal properties of this novel IFN-tau
are described in detail: structural characteristics of proteins
and genes, trophoblast expression, regulation of its expression,
structure of its gene promoter, its absence in human species and
in non-ruminant animals, the evolution of the IFN-tau genes, its
structure-function relationships with its three-dimensional
structure, structural localization of biological activities, its
lack of cytotoxicity and its receptor. Surprisingly, for an IFN,
IFN-tau is also a pregnancy-embryonic signal with paracrine
antiluteolytic activity. In order to maintain luteal progesterone
secretion, IFN-tau inhibits PGF-2alpha pulsatile secretion and
oxytocin uterine receptivity in early pregnancy. It is believed
to suppress pulsatile release of endometrial PGF-2alpha by
preventing oxytocin and estrogen receptor expression.
Additionally, it directly regulates prostaglandin metabolism and
possibly the PGE:PGF-2alpha ratio.
Publication Types:
Review
Review, Academic
PMID: 9865498 [PubMed - indexed for MEDLINE]
J Immunol 1998 Oct 1;161(7):3365-74
Steroid hormone regulation of cytokine secretion by proteolipid
protein-specific CD4+ T cell clones isolated from multiple
sclerosis patients and normal control subjects.
Correale J, Arias M, Gilmore W.
Department of Neurology, University of Southern California School
of Medicine, Los Angeles 90033, USA.
Steroid hormones have long been known to modulate immune
function, and recent studies indicate that one of the means by
which they do so involves effects on the secretion of
immunoregulatory cytokines. Our laboratory has found recently
that estradiol (E2) selectively modifies cytokine secretion in
proteolipid protein (PLP)-specific, CD4+ T cell clones isolated
from patients with the demyelinating disease, multiple sclerosis,
and from normal control subjects. The data suggest that E2 may
play a role in regulating the balance between pro- and
antiinflammatory conditions, especially at concentrations typical
of pregnancy. To determine whether other pregnancy-associated
steroid hormones are capable of similar activity, we expanded our
testing to include estrone (E1), estriol (E3), progesterone, and
dexamethasone. The results indicate that E1 and E3 enhance
secretion of Ag- or anti-CD3-stimulated IL-10 and IFN-gamma in
dose-dependent fashion, almost identical to that of E2. The
effect on IL-10 was more potent than occurred with IFN-gamma. In
addition, E1 and E3, like E2, had a biphasic effect on
TNF-alphabeta secretion, with low concentrations stimulatory, and
high doses inhibitory. None of the estrogens influenced IL-4 or
TGF-beta secretion. Progesterone enhanced secretion of IL-4,
without affecting any other tested cytokine. Finally,
dexamethasone induced TGF-beta secretion, but inhibited IFN-gamma
and TNF-alphabeta. This differential effect of steroid hormones
on the secretion of cytokines by CD4+ human T cell clones is
consistent with the possibility that, collectively, they promote
antiinflammatory conditions at high concentrations typical of
pregnancy.
PMID: 9759853 [PubMed - indexed for MEDLINE]
Inflamm Res 1998 Jul;47(7):290-301
Estrogen-mediated immunosuppression in autoimmune diseases.
Jansson L, Holmdahl R.
Section for Medical Inflammation Research, CMB, Lund University,
Sweden.
Gender affects the susceptibility to many autoimmune diseases.
Women have an increased risk of developing diseases such as
rheumatoid arthritis and multiple sclerosis compared with men.
The female preponderance is believed to depend in part on the
influence of sex hormones on the immune system. The mechanism of
estrogen-induced immune suppression both in human autoimmune
diseases and their experimental animal model counterparts is
discussed. In addition, the mechanisms of estrogen and
anti-estrogens are discussed in relation to their possible use as
future therapeutic anti-inflammatory agents.
Publication Types:
Review
Review, Academic
PMID: 9719493 [PubMed - indexed for MEDLINE]
N Engl J Med 1998 Jul 30;339(5):285-91
Comment in: N Engl J Med. 1998 Jul 30;339(5):339-40
Rate of pregnancy-related relapse in multiple sclerosis.
Pregnancy in Multiple Sclerosis Group.
Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P,
Moreau T.
European Database for Multiple Sclerosis Coordinating Center and
the Service de Neurologie, Hopital de l'Antiquaille, Lyons,
France.
BACKGROUND AND METHODS: Multiple sclerosis often occurs in young
women, and the effect of pregnancy on the disease is poorly
understood. We studied 254 women with multiple sclerosis during
269 pregnancies in 12 European countries. The women were followed
during their pregnancies and for up to 12 months after delivery
to determine the rate of relapse per trimester and the score on
the Kurtzke Expanded Disability Status Scale (range, 0 to 10,
with higher scores indicating more severe disability). The
relapse rate in each trimester was compared with the rate during
the year before the pregnancy. The effects of epidural analgesia
and breast-feeding on the frequency of relapse during the first
three months post partum and the disability score at 12 months
post partum were also determined. RESULTS: The mean (+/-SD) rate
of relapse was 0.7+/-0.9 per woman per year in the year before
pregnancy; it was 0.5+/-1.3 during the first trimester (P=0.03
for the comparison with the rate before pregnancy), 0.6+/-1.6
during the second trimester (P=0.17), and 0.2+/-1.0 during the
third (P<0.001). The rate increased to 1.2+/-2.0 during the first
three months post partum (P<0.001) and then returned to the
prepregnancy rate. The mean Kurtzke disability score worsened by
0.7 point during 33 months of follow-up, with no apparent
acceleration during the post-partum period. Neither
breast-feeding nor epidural analgesia had an adverse effect on
the rate of relapse or on the progression of disability in
multiple sclerosis. CONCLUSIONS: In women with multiple
sclerosis, the rate of relapse declines during pregnancy,
especially in the third trimester, and increases during the first
three months post partum before returning to the prepregnancy
rate.
Publication Types:
Multicenter Study
PMID: 9682040 [PubMed - indexed for MEDLINE]
Cell Immunol 1998 Jun 15;186(2):94-102
IFN-tau suppresses both the autoreactive humoral and cellular
immune responses and induces stable remission in mice with
chronic experimental allergic encephalomyelitis.
Mujtaba MG, Streit WJ, Johnson HM.
Department of Microbiology, University of Florida, Gainesville
32611, USA.
We have previously shown that interferon-tau (IFN-tau)
pretreatment inhibits the development of both acute and chronic
mouse experimental allergic encephalomyelitis (EAE), an animal
model for the human demyelinating disease multiple sclerosis
(MS). IFN-tau is a type I IFN that has pregnancy recognition
hormone activity in ruminants. Here we show that IFN-tau induced
remission in SJL/J mice that had ongoing chronic active EAE
disease and protected mice against secondary relapses. IFN-tau
treatment reversed lymphocyte infiltration and microglial
activation in the central nervous system. Mice that were treated
with IFN-tau had lower levels of anti-MBP antibodies than
untreated mice in both chronic and acute forms of EAE. MBP
induced proliferation in B cells from EAE mice, but treatment
with IFN-tau either in vivo or in vitro blocked activation.
Furthermore, IFN-tau inhibited MBP activation of T cells from EAE
mice. Thus, IFN-tau inhibits the humoral arm as well as the
cellular arm of the autoimmune disease EAE. The data presented
here show that IFN-tau inhibits both B cell and T cell responses
in EAE as well as active, chronic EAE, and this may help explain
the effectiveness of type I IFNs in treatment of MS.
PMID: 9665751 [PubMed - indexed for MEDLINE]
    KS