In-vitro secretion of proinflammatory cytokines by human amniochorion carrying hyper-responsive gene polymorphisms of tumour necrosis factor-alpha and interleukin-1beta.

The identification of polymorphisms in genes encoding proinflammatory cytokines that affect transcription or the secretion rate has opened new ways to understand the variation in responses to infection during pregnancy. In this study, human amniochorion carrying hyper-responsive alleles of tumour necrosis factor-alpha (TNF-alpha: TNF2 at -308) and interleukin-1beta (IL-1beta: IL-12 at +3953) were stimulated in vitro with bacterial lipopolysaccharide (LPS) and compared with tissues carrying the common alleles (TNF1 and IL-11). Fetal membranes carrying the TNF1 allele displayed an identical dose-response pattern to tissues carrying a TNF2 allele, except at the highest dose of LPS tested (50 ng/ml) there was a significantly greater production of TNF-alpha in the presence of a TNF2 allele. Membranes carrying the IL-12 polymorphism secreted IL-1beta in a dose-response curve that was different from IL-1* tissues when challenged with 5, 10 and 50 ng/ml LPS. These observations support the hypothesis that reproductive tissues carrying hyper-responsive proinflammatory cytokine genes may over-respond to intrauterine infection secreting higher amounts of cytokines, which in turn, may lead to adverse pregnancy outcomes.