Progesterone treatment reduces disease severity and increases IL-10 in experimental autoimmune encephalomyelitis

被引:90
作者
Yates, M. A. [1 ,2 ]
Li, Y. [1 ,2 ]
Chlebeck, P. [1 ]
Proctor, T. [1 ]
Vandenbark, A. A. [1 ,2 ,3 ]
Offner, H. [1 ,2 ,4 ]
机构
[1] Portland VA Med Ctr, Portland, OR USA
[2] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA
[3] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA
[4] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA
关键词
Progesterone; Estrogen; EAE; Multiple sclerosis; B cells; CENTRAL-NERVOUS-SYSTEM; CD8(+) T-CELLS; MULTIPLE-SCLEROSIS; DENDRITIC CELLS; ALPHA PRODUCTION; SPINAL-CORD; B-CELLS; ESTROGEN; MICE; EXPRESSION;
D O I
10.1016/j.jneuroim.2010.01.013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ovarian hormones, including progesterone, are known to have immunomodulatory and neuroprotective effects which may alter the disease course of experimental autoimmune encephalomyelitis (EAE). In the current study, we examined the treatment potential of progesterone beginning at the onset of EAE symptoms. Progesterone treated animals showed reduced peak disease scores and cumulative disease indices, and decreased inflammatory cytokine secretion (IL-2 and IL-17). In addition, increased production of IL-10 was accompanied by increased numbers of CD19+ cells and an increase in CD8+ cells. Decreased chemokine and chemokine receptor expression in the spinal cord also contributed to decreased lesions in the spinal cord. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:136 / 139
页数:4
相关论文
共 40 条
[1]   Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells [J].
Airas, L. ;
Saraste, M. ;
Rinta, S. ;
Elovaara, I. ;
Huang, Y. -H. ;
Wiendl, H. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2008, 151 (02) :235-243
[2]   Clonal expansions of CD8+ T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction [J].
Babbe, H ;
Roers, A ;
Waisman, A ;
Lassmann, H ;
Goebels, N ;
Hohlfeld, R ;
Friese, M ;
Schröder, R ;
Deckert, M ;
Schmidt, S ;
Ravid, R ;
Rajewsky, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (03) :393-404
[3]   Low-dose estrogen therapy ameliorates experimental autoimmune encephalomyelitis in two different inbred mouse strains [J].
Bebo, BF ;
Fyfe-Johnson, A ;
Adlard, K ;
Beam, AG ;
Vandenbark, AA ;
Offner, H .
JOURNAL OF IMMUNOLOGY, 2001, 166 (03) :2080-2089
[4]   Depletion of CD8+ cells abolishes the pregnancy protective effect of progesterone substitution with dydrogesterone in mice by altering the Th1/Th2 cytokine profile [J].
Blois, SM ;
Joachim, R ;
Kandil, J ;
Margni, R ;
Tometten, M ;
Klapp, BF ;
Arck, PC .
JOURNAL OF IMMUNOLOGY, 2004, 172 (10) :5893-5899
[5]   Inhibitory Effects of Progesterone Differ in Dendritic Cells from Female and Male Rodents [J].
Butts, Cherie L. ;
Bowers, Eve ;
Horn, J. Cash ;
Shukair, Shetha A. ;
Belyavskaya, Elena ;
Tonelli, Leonardo ;
Sternberg, Esther M. .
GENDER MEDICINE, 2008, 5 (04) :434-447
[6]   Failure to suppress the expansion of the activated CD4 T cell population in interferon γ-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis [J].
Chu, CQ ;
Wittmer, S ;
Dalton, DK .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) :123-128
[7]   Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus. The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective [J].
Ciriza, Iratxe ;
Carrero, Paloma ;
Frye, Cheryl A. ;
Garcia-Segura, Luis M. .
JOURNAL OF NEUROBIOLOGY, 2006, 66 (09) :916-928
[8]   Rate of pregnancy-related relapse in multiple sclerosis [J].
Confavreux, C ;
Hutchinson, M ;
Hours, MM ;
Cortinovis-Tourniaire, P ;
Moreau, T .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (05) :285-291
[9]   Immune sexual dimorphism: Effect of gonadal steroids on the expression of cytokines, sex steroid receptors, and lymphocyte proliferation [J].
De Leon-Nava, Marco A. ;
Nava, Karen ;
Soldevila, Gloria ;
Lopez-Griego, Lorena ;
Chavez-Rios, Jesus R. ;
Vargas-Villavicencio, Jose A. ;
Morales-Montor, Jorge .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2009, 113 (1-2) :57-64
[10]   Female sex steroids: effects upon microglial cell activation [J].
Drew, PD ;
Chavis, JA .
JOURNAL OF NEUROIMMUNOLOGY, 2000, 111 (1-2) :77-85