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.