LEAD DISRUPTS EICOSANOID METABOLISM, MACROPHAGE FUNCTION, AND DISEASERESISTANCE IN BIRDS

Lead (Pb) affects elements of humoral and cell-mediated immunity, and diminishes host resistance to infectious disease. Evidence is presente d supporting a hypothesis of Pb-induced immunosuppression stemming fro m altered fatty acid metabolism, and mediated by eicosanoids and macro phages (M empty set). Chronic Pb exposure increases the proportion of arachidonate (ArA) among fatty acids in Lipid from avian tissues, and this change provides precursors for eicosanoids, the oxygenated deriva tives of ArA that mediate M empty set acute inflammatory response. Ln the current study, we showed that the concentration of ArA in phosphol ipids of M empty set elicited from turkey poults fed 100 ppm dietary P b acetate was twice that of controls. In vitro production of eicosanoi ds by these M empty set was substantially increased, and this effect w as most pronounced following lipopolysaccharide stimulation: prostagla ndin F-2 alpha was increased 11-fold, thromboxane B-2 increased threef old, and prostaglandin E-2 increased by 1.5 times. In vitro phagocytic potential of these M empty set was suppressed, such that the percenta ge of M empty set engulfing sheep red blood cell (RBC) targets was red uced to half that of control M empty set. In vivo susceptibility of Pb -treated and control birds to Gram-negative bacteria challenge was als o evaluated. The morbidity of chicks inoculated with Salmonella gallin arum and fed either control or 200 ppm Pb acetate-supplemented diets w as similar, except early in the course of the disease when mortality a mong Pb-treated birds was marginally greater. In these studies, effect s of Pb that could influence immunological homeostasis were demonstrat ed for M empty set metabolism of ArA, for production of eicosanoids, a nd for phagocytosis. There was also the suggestion that these in vitro indices of immune function are related to in vivo disease resistance.