5-HYDROXYEICOSATETRAENOIC ACID BIOSYNTHESIS BY GESTATIONAL TISSUES - EFFECTS OF INFLAMMATORY CYTOKINES

OBJECTIVE: Our purpose was to determine whether inflammatory cytokines can modulate the production of arachidonate lipoxygenase metabolites by gestational tissues. STUDY DESIGN: Primary cultures of amnion, chorion, and decidual cells were incubated in the presence and absence of interleukin-1beta, 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. RESULTS: 5-Hydroxyeicosatetraenoic acid production was significantly increased by interleukin-1beta 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-1beta. CONCLUSIONS: Inflammatory cytokines generated in response to intrauterine infection may modulate uterine activity by stimulation of 5-hydroxyeicosatetraenoic acid biosynthesis.