Adaptive interactions between cytokines and the hypothalamic-pituitary-gonadal axis

Circulating and tissue concentrations of pyrogenic cytokines, especially interleukin (IL)-1β, vary temporally through the menstrual cycle and pregnancy. The secretion of these cytokines in vitro by isolated human mononuclear cells is significantly influenced by exogenous gonadal steroids and gonadotropins. Reciprocally, cytokines influence gonadotropin secretion by the pituitary and steroidogenesis by the ovaries and testes. Several hypotheses have been advanced regarding the adaptive value of these interrelationships. Cytokine-induced synthesis of proteolytic enzymes and extracellular matrix proteins may be important for the tissue remodeling necessary for ovulation, inplantation, and delivery. Tolerance of the fetal allograft may require down-regulation of cytotoxic effector cells and reciprocal upregulation of humoral and nonspecific host defenses. The inhibitory influence of IL-1β on the luteinizing hormone surge may prevent inopportune conception, and the abortive influences of tumor necrosis factor-α and gamma interferon may terminate pregnancy during periods of infection.