IL-3 and IL-5 enhance the production of LTB4 stimulated by calcium ionophore in rat basophilic leukemia cells.

To determine the regulatory mechanism of Leukotriene (LT) B4 synthesis by cytokines, we investigated the regulation of LTB4 generation by short-term (30 min) priming and long-term (15 h) enzyme-inducing actions of the four cytokines interleukin (IL)-3, IL-5, tumor necrosis factor alpha (TNF-alpha), and transforming growth factor alpha (TGF-alpha) in rat basophilic leukemia-1 (RBL-1) cells. Pretreatment of cells with IL-3 or IL-5 for 30 min increased A23187- (5x10(-9)M) stimulated synthesis of LTB4 by three to four times over control levels. However, IL-3 or IL-5 lacked this effect when stimulated with exogenous arachidonic acid A at 10(-4)M. TNF-alpha and TGF-alpha had no priming effect on LTB4 synthesis following stimulation with either A23187 (5x10(-9)M) or AA(10(-4)M). Stimulation with the calcium ionophore (A23187)(10(-5)M) or AA(10(-4)M) following 15-h exposure to these cytokines had no effect. These results suggest that IL-3 and IL-5 increase the production of LTB4 by priming the activity of phospholipase A2(PLA2) without inducing enzymes in the arachidonate 5-lipoxygenase pathway. Such a priming effect may be important in regulating the development of allergic and other diseases involving the inflammatory reaction.