Pre-term labor: an intra-uterine inflammatory response syndrome?

Abstract

Emerging concepts of sepsis suggest that the host response to an infectious stimulus results in some cases of uncontrolled release of inflammatory cytokines leading to signs of sepsis. Systemic inflammatory response syndrome (SIRS) has been suggested as a diagnosis when no etiologic organism can be found. Infection may account for up to 30% of cases of pre-term labor, and may either be clinically-evident or sub-clinical. Inflammatory cytokines can be detected in elevated concentrations in the amniotic fluid and plasma of women with pre-term labor, and human gestational tissues are potentially rich sources of inflammatory cytokines, as found in in vivo and in vitro studies. Also, maternal decidua and fetal membranes produce mRNA for inflammatory cytokines in the setting of infection-associated pre-term labor and normal term labor. Notably, anti-inflammatory cytokines, such as interleukin-10 (IL-10) do not appear to be present in substantial quantities in these pathophysiologic and physiologic conditions. Animal models indicate that pre-term labor can be stimulated by bacteria, bacterial cell wall products, and inflammatory cytokines such as IL-1 and tumor necrosis factor. These findings suggest that: (1) infectious stimuli may result in the liberation of inflammatory cytokines from gestational tissues leading inevitably to pre-term labor and delivery; (2) inhibition of this process may either be overcome or abrogated, and (3) the mechanisms regulating cytokine production in maternal and fetal tissues are disturbed. Thus, pre-term labor associated with sub-clinical infection may result in a dysregulated local inflammatory response, in which the maternal host response causes an 'intra-uterine inflammatory response syndrome' leading to pre-term labor and delivery.