IL-3 AND IL-5 ENHANCE THE PRODUCTION OF LTB(4) STIMULATED BY CALCIUM IONOPHORE IN RAT BASOPHILIC LEUKEMIA-CELLS

To determine the regulatory mechanism of Leukotriene (LT) B-4 synthesi s by cytokines, we investigated the regulation of LTB(4) generation by short-term (30 min) priming and long-term (15 h) enzyme-inducing acti ons of the four cytokines interleukin (IL)-3, IL-5, tumor necrosis fac tor alpha (TNF-alpha), and transforming growth factor alpha (TGF-alpha ) in rat basophilic leukemia-1 (RBL-1) cells, Pretreatment of cells wi th IL-3 or IL-5 for 30 min increased A23187- (5 x 10(-9) M) stimulated synthesis of LTB(4) by three to four times over control levels. Howev er, IL-3 or IL-5 lacked this effect when stimulated with exogenous ara chidonic acid A at 10(-4) M. TNF-alpha and TGF-alpha had no priming ef fect on LTB(4) synthesis following stimulation with either A23187 (5 x 10(-9) M) or AA (10(-4) M). Stimulation with the calcium ionophore (A 23187) (10(-5) M) or AA (10(-4) M) following 15-h exposure to these cy tokines had no effect. These results suggest that IL-3 and IL-5 increa se the production of LTB(4) by priming the activity of phospholipase A (2) (PLA(2)) without inducing enzymes in the arachidonate 5-lipoxygena se pathway. Such a priming effect may be important in regulating the d evelopment of allergic and other diseases involving the inflammatory r eaction.