INDUCTION OF 15-LIPOXYGENASE BY INTERLEUKIN-13 IN HUMAN BLOOD MONOCYTES

15-lipoxygenase (15-LO) catalyzes hydroperoxidation of fatty acids, a reaction of potential relevance to inflammation, membrane remodeling, and atherosclerosis. In human leukocytes, 15-lipoxygenation of arachid onic acid produces 15-(S)hydroxyeicosatetraenoic acid and lipoxin A4, which suppress white cell chemotaxis, adherence, and activation, and a ntagonize proinflammatory leukotrienes. Interleukin (IL)-13, produced by T-helper subset 2 (TH-2) lymphocytes, specifically and potently ind uced 15-LO gene expression and enzyme activity in human monocytes. Amo ng other TH-2 lymphokines, this induction of 15-LO is shared by IL-4 b ut not by IL-10. Interferon-gamma, a product of TH-1 lymphocytes, bloc ked IL-13-mediated induction of 15-LO. The induction of the anti-infla mmatory 15-LO pathway by IL-13 reveals a new facet of IL-13 biology th at supports its role as a cytokine with potential to down-regulate inf lammatory pathways. The contrasting effects of interferon-gamma and IL -13 on 15-LO induction demonstrate mechanisms by which T-lymphocyte su bsets may modulate macrophage/monocyte function in inflammation or ath erosclerosis.