Inflammatory cytokines in a murine model of infection-induced preterm labor: Cause or effect?

OBJECTIVE: To characterize the expression of inflammatory cytokines in a murine model of preterm in delivery induced by heat-killed bacteria. METHODS: The right uterine horns of female CD-1 mice on day 14.5 of 19-20 days of gestation were inoculated with either sterile media or Killed Escherichia coli bacteria (10(5)-10(10) organisms per mouse). The incidence of preterm delivery tt,as recorded. The concentrations of cytokines (interleukin [IL-] 1 alpha, IL-1 beta, IL-1 receptor antagonist [IL-1ra] IL-6, and tumor necrosis factor alpha [TNF alpha]) within maternal and fetal tissue homogenates were determined by enzyme-linked immunosorbent assay at various times after inoculation. RESULTS: Killed E. coli induced preterm delivery in a dose-dependent fashion. Inoculation with 10(10) bacteria (sufficient to cause delivery, in all mice) produces increases in IL-1 alpha, IL-1 beta, IL-6, and TNF alpha within uteri and fetal membranes, but Mat within placentas, fetal bodies, and maternal serum. Maximum lean uterine levels of IL-1 and IL-6 exceeded those of fetal tissues (membranes, placentas, and fetal bodies) by greater than 15-fold. Maximal uterine IL-1 and TNF alpha levels following inoculation with 10(10) bacteria exceeded those that followed inoculation with 10(7) bacteria (below the threshold for delivery) by 2.5- to 5-fold. The anti-inflammatory cytokine IL-1ra was expressed in higher concentrations in fetal than in maternal tissues and was unaltered by the bacterial inoculum. CONCLUSIONS: E. coli induce labor in mire evert in the absence of bacterial viability. Although IL-1 and TNF alpha were upregulated by bacterial inocula causing a delivery, peak levels were only 2.5- to 5-fold higher than those that occurred with inocula below the threshold for delivery (1000-fold fewer bacteria). Whether IL-l and TNF alpha mediate labor during in vivo infection, or whether the upregulation of these cytokines merely represents an epiphenomenon accompanying infection, remains unknown. Copyright (C) 1999 by the Society for Gynecologic Investigation.