Human placental cells show enhanced production of interleukin (IL)-8 in response to lipopolysaccharide (LPS), IL-1 and tumour necrosis factor (TNF)-alpha, but not to IL-6

Interleukin-8 (IL-8) is a chemotactic and activating factor for neutrophils which play important roles in host defence mechanisms. The human placenta constitutively produces IL-8 during pregnancy and enhances its production i n chorioamnionitis. The present study was designed to investigate in vitro the regulatory mechanism for IL-8 production in the placentas in normal and inflammatory states. Placental cells produced IL-8 in a dose-dependent fas hion when stimulated with lipopolysaccharide (LPS). The purified trophoblas ts showed significantly higher IL-8 production than untreated placental cel ls. The expression of IL-8 gene in the trophoblasts in the third trimester was observed by reverse transcription-polymerase chain reaction (RT-PCR). T he placental cells also release IL-8 in a dose-dependent manner, in respons e to r-(recombinant) IL-1 alpha and tumour necrosis factor (TNF)-alpha, but not rIL-6. Moreover, LPS-activated placental cells spontaneously produced a much larger amount of IL-8 and showed increased responses to rIL-1 alpha and TNF-alpha. It may, therefore, be proposed that placental cells with mul tiple endocrine functions exert immunological functions by constitutive pro duction of IL-1 and TNF-alpha, which stimulate placental IL-8 release. This cytokine cascade in the placenta may be augmented by LPS in chorioamnionit is, thereby potentiating the fete-maternal defence mechanisms against infec tion.