Consistent production of a higher TH1:TH2 cytokine ratio by stimulated T cells in men compared with women

Abstract

Objective: To evaluate the T helper 1 (T H 1)/T helper 2 (T H 2) lymphocyte cytokine pro®les in women and men and to study the in vitro effects of sex hormones on lymphocyte secretion of cytokines. Methods: Analysis of serum concentration and lymphocyte synthesis of T H 1 (gamma interferon (INF-g) and interleukin 2 (IL-2)) and T H 2 (interleukin 4 (IL-4) and interleukin 10 (IL-10)) cytokines was performed in 20 women and 15 men. Analysis of modi®cations in cytokine secretion induced by supplementation of lymphocyte culture with increasing concentrations of sex hormones was carried out. Results: Higher levels of INF-g and IL-2 and lower levels of IL-4 and IL-10 were detected in the phytohemagglutinin-stimulated lymphocyte culture supernatants of men compared with women; the INF-g:IL-4 ratio was signi®cantly higher in men. In women, similar concentrations of all the cytokines were detected in culture supernatants obtained during the follicular and the luteal phases. The addition of sex hormones did not modify the concentration of cytokines in supernatants of phytohemagglutinin-stimulated T-cell cultures.Conclusions: Women present a predominant T H 2 cytokine pro®le, which could be involved in immune responses characterized principally by the secretion of antibodies. This could be a factor implicated in the higher concentration of immunoglobulins or the increased prevalence of autoimmune diseases detected in females.

Cutting Edge: Cross-Regulation by TLR4 and T cell Ig Mucin-3 Determines Sex Differences in Inflammatory Heart Disease

“…Males had significantly increased numbers of monocyte/macrophages, granulocytes, MC, and dendritic cells (DC), whereas females had significantly increased numbers of B cells in the heart (Fig. 1C) consistent with the robust Ab response known to occur in female mice and humans (12).…”

Dehydroepiandrosterone improves the ovarian reserve of women with diminished ovarian reserve and is a potential regulator of the immune response in the ovaries

“…These steroids interact critically with immune function. Estrone can shift the female immune system to a Th2-type response in the luteal phase, whereas postmenopausal women often exhibit enhanced Th1 cytokines (66). As mentioned previously, DHEA can restore PBMC function and increase the ability of human PBMCs to release pro-inflammatory cytokines after surgery via the estrogen receptor; this immunomodulatory effect of DHEA appears to be connected to estrogen receptors (55).…”

Peroxisome proliferator-activated receptor (PPAR)α and -γ regulate IFNγ and IL-17A production by human T cells in a sex-specific way

“…Female myelin-specific T cells produce more IFNγ and less Th2 cytokines than male T cells and are more encephalitogenic upon adoptive transfer (9)(10)(11). However, despite numerous attempts to explore this issue in humans (12)(13)(14)(15)(16), conclusive evidence in support of a Th1 bias in women is lacking.…”