Immunoendocrinology of preterm labor: the link between corticotropin-releasing hormone and inflammation.

Preterm labor is the final common pathway after several potential insults to the uterus or fetus. The preterm labor syndrome may be precipitated by several different pathophysiologic events, including intrauterine infection, uterine ischemia, uterine overdistention, hormonal disturbances, and other problems. Intrauterine infections (both clinically evident and subclinical) are associated with increased amniotic fluid concentrations of proinflammatory cytokines, and gestational tissues and the fetus are potential sources of these cytokines. In addition to culture-proven intrauterine infection, there may be an "intrauterine inflammatory response syndrome" that could account for cases of preterm labor in which no infectious organism can be identified. Because the immunologic and endocrinologic systems regulate each other extensively, there is potential for corticotropin-releasing hormone to regulate inflammatory responses and vice versa. The cytokine interleukin 1 stimulates production of corticotropin-releasing hormone, and corticotropin-releasing hormone in turn regulates cytokine production by immune effector cells. Because maternal stress is associated with preterm birth, abnormalities in the regulation of corticotropin-releasing hormone and the production of inflammatory cytokines may be a mechanism that could form the pathophysiologic basis for this association.