IL-1α but not IL-1β-induced prostaglandin synthesis is inhibited by corticotropin-releasing factor

Interleukin (IL)-1α and IL-1β share low amino acid homology, but exhibit a very similar array of biological activities. The authors previously showed negative regulation of IL-1α-induced prostaglandin (PG) production by corticotropin releasing factor (CRF). In this study, the authors compared the effect of CRF on IL-1α- and IL-1β-induced PG synthesis. IL-1α (100 U/ml) increased prostacyclin (PGI₂) (measured as 6-keto PGF(1α) [6K]) synthesis in endothelial cells and the production of PGE₂ in fibroblasts. The PG response to IL-1α was suppressed by simultaneous exposure to CRF (2.5 x 10^-11-2.5 x 10^-8 M) in both cell types. IL-1α enhanced both phospholipase A₂ (PLA₂) and prostaglandin H synthase (PGHS) activities, and the two effects were completely abrogated by CRF. IL-1β (100 U/ml) was as active as IL-1α in triggering release of PGI₂ from endothelial cells and PGE₂ from fibroblasts. However, CRF (2.5 x 10^-11-2.5 x 10^-8 M) failed to alter the IL-1β-induced PG synthesis in both cell types. Following IL-1β PGHS activity, and to a lesser extent PLA₂ activity, were enhanced, however CRF only inhibited PGHS and not PLA₂ activity. It is concluded that although IL-1α and IL-1β usually produce similar biological effects, here they seem to act via different mechanisms. The different regulation of IL-1α and IL-1β pro-inflammatory activities by CRF may attribute special precision and specificity to the neuroendocrine-immune control of inflammatory processes.