The effect of progesterone and estrogen on proinflammatory cytokine costimulatory proliferative activity



The lymphocyte proliferation is multicomponent mechanism of immune system reactivity. Proinflammatory cytokines enhance proliferation of activated lymphocytes. Progesterone (P) and 17β-estradiol (E2) inhibit proliferation of mitogen and alloantigen- activated lymphocytes. This work is to study the effect of P and E2 on costimulatory proliferative activity (CPA) of TNF, IL-1α/βin vitro.

Separated mononuclear cells from peripheral male blood were incubated in the presence of antiCD3 Ab, TNF or IL-1α/β, P (2 mcg/mL), E2 (0.2 mcg/mL). Proliferation was determined by standard 3H-thymidine incorporation assay. P and E2 inhibited lymphocyte response to antiCD3 antibody. P had a stronger effect than E2 (64 and 13% of inhibition). TNF increased antiCD3-induced proliferation of lymphocytes by 24%, IL-1α by 16%, IL-1β by 19%. E2 enhanced the TNF–CPA, P neutralized this TNF-induced effect and reverted it (inhibition of lymphocytes proliferation was enhanced in the presence 0.1-2.5 ng/mL TNF). We found dominant inhibitory effect of P on the TNF-CPA when P and E2 were added simultaneously. CPA of IL-1α/β was down-regulated by P and E2.

Thus P and E2 had opposite effects on TNF–CPA (E2 enhanced it while P neutralized it) and down-regulated CPA of IL-1α/β. P alone or in combination with E2 showed dominant inhibitory effect on CPA of TNF, IL-1α/β. Our results suggest possible roles for P and E2 as regulators of activity of proinflammatory cytokines and their functions in lymphocyte proliferation.