INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR STIMULATE ARACHIDONIC-ACID RELEASE AND PHOSPHOLIPID-METABOLISM IN HUMAN MYOMETRIAL CELLS

OBJECTIVE: Our aim was to evaluate the effects of the cytokines interl eukin-1 and tumor necrosis factor on arachidonic acid release in human myometrial cells. STUDY DESIGN: Primary monolayer cultures of human m yometrial cells prelabeled with tritiated arachidonic acid were expose d to interleukin-1 or tumor necrosis factor for varying periods and th e release of tritiated arachidonic acid and its loss from phospholipid s were measured by radiochromatography. To gain some information on th e biologic action of interleukin-1 the contractile response to oxytoci n was measured in myometrial strips preincubated with this cytokine. D ata were statistically evaluated with analysis of variance or Student' s t test. RESULTS: Both cytokines caused a dose-dependent increase in tritiated arachidonate release that was suppressed by the protein synt hesis inhibitor cycloheximide. Tritiated arachidonic acid release was maximal after 24 hours of stimulation with interleukin-1. Both interle ukin-1 and tumor necrosis factor stimulated the release of the isotopi cally labeled fatty acid from phosphatidylcholine. In addition, interl eukin-1 also increased the loss of arachidonic acid from phosphatidic acid and significantly potentiated the oxytocin-evoked myometrial cont ractility. CONCLUSIONS: Both interleukin-1 and tumor necrosis factor e nhance arachidonic acid release, probably by inducing the synthesis of phospholipase A, and possibly other enzymes involved in the metabolis m of phospholipids. In turn, arachidonic acid itself may act as a seco nd messenger, synergizing with other uterotonic agents, as well as ser ving as the precursor for prostaglandins and various other bioactive e icosanoids.