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Leukotriene B4 and lnterleukin-8 in Human Immunodeficiency Virus-related Pulmonary Disease (9)

Leukotriene B4 and lnterleukin-8 in Human Immunodeficiency Virus-related Pulmonary Disease (9)Discussion
Despite recent growing interest in the biology of P carinii and pathophysiology of P carinii pneumonia, little is known of the pathogenesis of lung injury in this disease. Similarly, the pathogenesis of NIP, a frequent cause of respiratory symptoms in patients with HIV infection, remains obscure. Several groups have suggested that cytokines, particularly tumor necrosis factor a, play a role in AIDS-related lung diseases. Kernbaum et al proposed a role for phospholipase-induced damage in P carinii pneumonia. Several investigators have shown that BAL neutrophilia in P carinii pneumonia confers a poor prognosis and identifies a group of patients with more severe disease, suggesting that neutrophil-mediated damage contributes to lung injury.

Finally, the efficacy of corticosteroids in the treatment of P carinii pneumonia implies that a host inflammatory response contributes to lung injury. In an attempt to further define the role of neutrophils in P carinii pneumonia and NIP, we have measured two potent neutrophil chemotaxins, LTB4 and IL-8, in BAL fluid from patients with these conditions. In addition, we have measured BAL fluid PLAg activity, since PLAa itself has been implicated as a mediator of lung injury. While the finding of elevated levels of an inflammatory mediator in BAL fluid does not demonstrate causality, these data can suggest pathogenetic mechanisms and guide further research.

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