THE EFFECT OF INHIBITION OF LEUKOTRIENE SYNTHESIS ON THE ACTIVITY OF INTERLEUKIN-8 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

THE cytokines interleukin-8 (IL-8) and granulocyte-macrophage colony-s timulating factor (GM-CSF) enhanced the extracellular release of arach idonate metabolites from ionophore-stimulated neutrophils by 145 +/- 1 0% (mean +/- S.E.M., n = 13) and 182 +/- 11% (n = 16), respectively. T o determine whether enhanced leukotriene production mediates the effec ts of these cytokines on neutrophil activity, two different specific a rachidonate 5-lipoxygenase (5-LO) inhibitors, piriprost and MK-886, we re used to inhibit leukotriene synthesis. Neither inhibitor affected t he upregulation of CD11b beta2-integrin expression or priming of super oxide generation stimulated by IL-8 and GM-CSF. It is concluded that l eukotrienes do not mediate either the direct or priming effects of the se cytokines and that these classes of anti-inflammatory drugs are the refore unlikely to inhibit the effects of IL-8 and GM-CSF on neutrophi l activation.