Recombinant interleukin-1 beta stimulates eicosanoid production in rat primary culture astrocytes

Astrocytes may play a prominent role in the initiation of immunoinflammatory responses in the central nervous system. They can be induced to synthesize eicosanoids but how immunologically relevant molecules modulate this process is not known. We examined the influence of recombinant interleukin-1 (rIL-1), an immunomodulating monokine on the release of arachidonic acid metabolites. IL-1 (1-30 U) induced a dose-related elaboration predominantly of the cyclo-oxygenation products prostaglandin E and thromboxane B2. Preincubation of rIL-1 with a specific antibody abrogated and heat-inactivation destroyed this activity. Both mepacrine and the isoquinolinesulfonamide H7 blocked the stimulatory effect dose-dependently, indicating involvement of protein kinase C in this novel biologic activity of IL-1. In central nervous system inflammation, IL-1-evoked release from astrocytes of arachidonic acid-derived metabolites may influence the severity of phlogistic responses and modulate local immune reactivity.