Enhanced tumor necrosis factor-alpha-specific and decreased interleukin-10-specific immune responses to LPS during the third trimester of pregnancy in mice

It is increasingly apparent that there is a bidirectional interaction betwe en the maternal immune system and the reproductive system during pregnancy. Pregnancy is associated with a suppression of maternal specific immune res ponses, which process underlies the protection of fetal tissues expressing paternally inherited alloantigens. However. recent evidence indicates that the suppression of specific, lymphocyte-mediated immune responses during pr egnancy is accompanied by activation of the nonspecific arm of the maternal immune response. In the present study, we have investigated the effect of pregnancy on the non-specific immune response induced by bacterial lipopoly saccharide (LPS, endotoxin) in mice, Pregnancy enhanced the LPS-induced pro duction of proinflammatory cytokines, including tumor necrosis factor-alpha , interleukin (IL)-6, and interferon-gamma. On the other hand, LPS-induced levels of the anti-inflammatory cytokine IL-10 were suppressed in pregnant mice. These alterations in cytokine production correlated with an increased susceptibility for endotoxemic mortality in the pregnant mice. Although ad renergic receptors are important regulators of cytokine production in non-p regnant mice, the alpha (2) and the beta -adrenoceptor-mediated modulation of cytokine production ceases to operate during pregnancy associated with s evere endotoxemia. These data may explain how excessive activation of the n on-specific immune responses during pregnancy can contribute to the increas ed severity of some maternal diseases, including septic shock, and can be a ll important pathophysiological factor in disseminated intravascular coagul ation or preeclampsia.