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Leukotriene B4 and lnterleukin-8 in Human Immunodeficiency Virus-related Pulmonary Disease (2)

The demonstration of phospholipase activity in bronchoalveolar secretions of experimental animals with P carinii pneumonia, whether derived from host or organism, suggests several possible mechanisms of cellular injury. Phospholipase Ag (PLAJ hydrolyzes membrane phospholipids, producing membrane-damaging lysophospholipids and free fatty acids, and has been implicated in the pathogenesis of adult respiratory distress syndrome. PLA action also liberates arachidonate, which is metabolized to potent proin-flammatory substances, the eicosanoids. Among the eicosanoids, leukotriene B4 (LTB4) is a potent neutrophil chemotaxin in vivo and in vitro, and may play a role in the lung injury of adult respiratory distress syndrome, bacterial pneumonia, and asbestosis. Interleukin-8 (IL-8), a cytokine produced principally by mononuclear phagocytes but also by alveolar epithelial cells, is another potent neutrophil chemotaxin and activator. Interleuldn-8 has been implicated in the pathogenesis of adult respiratory distress syndrome and idiopathic pulmonary fibrosis,- and may be the major neutrophil chemotactic factor in the lung.
We have measured LTB4, IL-8, and PLAg activity in BAL fluid from HIV-infected patients with P carinii pneumonia and NIP as well as from asymptomatic HIV-positive patients and normal volunteers and correlated these markers of acute inflammation with clinical and laboratory evidence of the severity of respiratory disease. These observations should help to define the role of these inflammatory mediators in the pathogenesis of HIV-related lung disease.

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