Effect of estrogen on Th1, Th2 and Th17 cytokines production by proteolipid protein and PHA activated peripheral blood mononuclear cells isolated from multiple sclerosis patients.
OBJECTIVE
A large body of studies has shown that 17-β estradiol (E2) has a protective effect on susceptibility to experimental autoimmune encephalomyelitis (EAE). Clinical improvement in multiple sclerosis and its animal model, EAE, during pregnancy, when estrogen levels are high, suggests an immunomodulatory role for estrogens. The immune basis for this protection is poorly understood. In this study we evaluated the effect of E2 on the synthesis of inflammatory, antiinflammatory and regulatory cytokines.


METHODS
We analyzed the effect of E2 on IL-4, IL-10, IL-17, TNF-α and IFN-γ cytokines produced by proteolipid protein (PLP) or mitogen phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells isolated from multiple sclerosis patients in comparison to healthy control group. We used RT-PCR and ELISA to detect the level of cytokines.


RESULTS
We found that E2 significantly increased IL-10 expression and secretion and decreased expression of TNF-α in both groups and IL-4 in patients in cells stimulated with PLP or PHA (p <0.0001).


CONCLUSIONS
These data indicated that E2 could affect expression and secretion of inflammatory and anti-inflammatory cytokines and could regulate immune responses especially in the differentiation towards regulatory responses, and this finding might have therapeutic value in multiple sclerosis.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Iran.
Ani
A
Javadian
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Iran.
Eisa
E
Salehi
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Iran.
Katayon
K
Bidad
MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad Ali
MA
Sahraian
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Iran. Electronic address: izadm@sina.tums.ac.ir.
Maryam
M
Izad
D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D016207:Cytokines; D004967:Estrogens; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D004958:Estradiol; D007371:Interferon-gamma
17-β estradiol; Estrogen; Multiple sclerosis; Regulatory T cells; Th1; Th17; Th2