Interleukin-1 beta deficiency results in reduced NF-kappa B levels in pregnant mice

Interleukin (IL)-1 beta-deficient (IL-1 beta(-/-)) mice were assessed for c ytokine production during pregnancy. A significant reduction in nuclear fac tor (NF)-kappa B p65 protein content was observed in the uteri and spleens of pregnant IL-1 beta(-/-) mice, as demonstrated by immunohistochemistry an d Western immunoblot analysis. In addition, electromobility gel shift assay revealed less DNA binding activity of NF-kappa B p65-containing complex in pregnant IL-1 beta(-/-) mice. To investigate differences in cytokine produ ction regulated by NF-kappa B, the levels of tumor necrosis factor-alpha, m acrophage inflammatory protein-1 alpha, and interferon-gamma were measured in the uterine wall, spleen homogenates, and spleen cell cultures obtained from pregnant mice. Endocervical administration of lipopolysaccharide (LPS) increased cytokine levels in both wild-type (IL-1 beta(+/+)) and IL-1 beta (-/-) animals, but in IL-1 beta(-/-) mice this response was 50-75% lower. S plenocytes from nonpregnant mice exhibited decreased LPS-induced cytokine p roduction when primed in vitro with progesterone. This suppression was 25% greater in IL-1 beta(-/-) than in IL-1 beta(+/+) mice. These data suggest t hat constitutive NF-kappa B p65 protein synthesis is regulated by IL-1 beta , particularly during pregnancy.