Effects of cytokines on prostaglandin production and steroidogenesis of incubated preovulatory follicles of the rat.

Cytokines, leukocyte-derived peptide regulators of inflammation and other lympho-hematopoietic processes, have been implicated in ovarian physiology on the basis of findings of cytokines in follicular fluids and the presence of leukocytes in ovarian tissue. During the dramatic tissue remodelling at ovulation, several inflammatory mediators play pivotal roles in the occurrence of follicular rupture, but no data exist regarding the involvement of cytokines in this process. In the present study we have examined the effects of three different lymphocyte- and macrophage-derived cytokines--tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and interleukin-2 (IL-2)--on the production of ovulatory mediators such as prostaglandins and progesterone in the preovulatory follicle of the eCG/hCG-primed immature rat. Preovulatory follicles were incubated in the presence of human recombinant cytokines for up to 24 h, and the concentrations of prostaglandins and steroids in the incubation medium were measured by RIAs. TNF alpha and IL-1 beta stimulated production of prostaglandin E and prostaglandin F2 alpha in a dose-dependent manner during a 24-h incubation. Synthesis of prostacyclin was also stimulated by TNF alpha and IL-1 beta, as indicated by high levels of its stable metabolite 6-keto-prostaglandin F1 alpha. Time-course studies showed that a major portion of the prostaglandins were produced between 12 and 24 h. IL-2 was without effect on these parameters. TNF alpha and IL-1 beta also dose-dependently increased the production of progesterone and this was not inhibited by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)