Interleukin-1 potentiates bradykinin- and TNFα-induced PGE2 release

The ability of interleukin-1 (IL-1α), IL-1β, tumour necrosis factor α (TNFα) and bradykinin to cause prostaglandin E2 (PGE2) release from human synovial cells was exmained. IL-1α and IL-β proved equipotent in their effect, and were up to four orders of magnitude more potent than TNFα after incubation for 24 h. Bradykinin proved the weakest of all the agonists examined. When the cells were pretreated with IL-1α or IL-1β for 24 h, their ability to release PGE2 in response to a short incubation (1 h) with bradykinin, TNFα or a second dose of IL-1 was potentiated. In addition, TNFα and bradykinin were shown to increase the level of free arachidonic acid (AA) in the cells. Furthermore, a similar potentiation in the response of pretreated cells was observed with exogenous AA. It is already known that pretreatment with IL-1 for 24 h results in an induction of cyclo-oxygenase (CO). It seems likely, therefore, that activation of phospholipase A2 which occurs during as short incubation with IL-1, TNFα or bradykinin releases substrate, AA, which is more rapidly converted to PGE2 by cells in which CO has been induced. The result of these events might indicate a sustained release of PGE2 at sites of inflammation where such mediators are released.