Leukotriene B₄ and interleukin-8 in human immunodeficiency virus-related pulmonary disease

Study objective: To investigate the pathogenesis of lung injury in Pneumocystis carinii pneumonia and nonspecific interstitial pneumonitis (NIP), common pulmonary complications of human immunodeficiency virus (HIV) infection. The efficacy of corticosteroid therapy in P carinii pneumonia and the observation that bronchoalveolar lavage (BAL) neutrophilia predicts a poor prognosis support the premise that the lung injury of P carinii pneumonia is due to the host's inflammatory response to the infection. Design: In vitro measurements on previously collected BAL fluid samples. Setting: The Clinical Center of the National Institutes of Health, a research hospital and tertiary care referral center. Patients: Five normal volunteers, 5 asymptomatic HIV-positive patients, 10 HIV-positive patients with NIP (5 asymptomatic and 5 with respiratory symptoms), and 19 HIV-positive patients with P carinii pneumonia. Measurements and results: BAL leukotriene B₄ (LTB₄), interleukin 8 (IL-8), and phospholipase A₂ (PLA₂) were measured. IL-8 and PLA₂ were elevated in patients with P carinii pneumonia, and IL-8 correlated with BAL fluid absolute neutrophil count. LTB₄, IL-8, and PLA₂ levels were elevated in patients with NIP; LTB₄ and PLA₂ levels correlated with absolute neutrophil count, and IL-8 correlated with alveolar-arterial oxygen pressure difference. IL-8 was elevated in the asymptomatic HIV- positive patients, and there was a trend toward elevation of PLA₂ in this group. Conclusion: IL-8 appears to play a role in the pathogenesis of lung injury in P carinii pneumonia and may be the principal neutrophil chemotaxin in this disease; PLA₂ may also be involved in the pathogenesis of P carinii pneumonia. Both LTB₄ and IL-8 may be involved in the recruitment of neutrophils and subsequent lung injury of NIP. These data suggest that there are varying mechanisms by which inflammatory cells are recruited to the lung in different HIV-related lung diseases.