5-Hydroxyeicosatetraenoic acid biosynthesis by gestational tissues: effects of inflammatory cytokines.

Abstract

Our purpose was to determine whether inflammatory cytokines can modulate the production of arachidonate lipoxygenase metabolites by gestational tissues. Primary cultures of amnion, chorion, and decidual cells were incubated in the presence and absence of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6. Supernatants were assayed for leukotriene B4, leukotriene C4, 5-, 12- and 15-hydroxyeicosatetraenoic acid by means of specific radioimmunoassays. Cellular proteins were determined. 5-Hydroxyeicosatetraenoic acid production was significantly increased by interleukin-1 beta and interleukin-6 treatment in amnion, chorion, and decidual cells. Tumor necrosis factor-alpha elicited a modest increase, which was not statistically significant, in mean 5-hydroxyeicosatetraenoic acid production by these cells. Production rates of leukotrienes B4 and C4 and 12 and 15-hydroxyeicosatetraenoic acid were not affected by treatment with interleukin-1 beta. Inflammatory cytokines generated in response to intrauterine infection may modulate uterine activity by stimulation of 5-hydroxyeicosatetraenoic acid biosynthesis.