LEUKOTRIENE-B4 AND INTERLEUKIN-8 IN HUMAN IMMUNODEFICIENCY VIRUS-RELATED PULMONARY-DISEASE

Study objective: To investigate the pathogenesis of lung injury in Pne umocystis carinii pneumonia and nonspecific interstitial pneumonitis ( NIP), common pulmonary complications of human immunodeficiency virus ( HIV) infection. The efficacy of corticosteroid therapy in P carinii pn eumonia and the observation that bronchoalveolar lavage (BAL) neutroph ilia predicts a poor prognosis support the premise that the lung injur y 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 Instit utes of Health, a research hospital and tertiary care referral center. Patients: Five normal volunteers, 5 asymptomatic HIV-positive patient s, 10 HIV-positive patients with NIP (5 asymptomatic and 5 with respir atory 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 e levated 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 a bsolute neutrophil count, and IL-8 correlated with alveolar-arterial o xygen pressure difference. IL-8 was elevated in the asymptomatic HIV-p ositive patients, and there was a trend toward elevation of PLA2 in th is group. Conclusion: IL-8 appears to play a role in the pathogenesis of lung injury in P carinii pneumonia and may be the principal neutrop hil chemotaxin in this disease; PLA2 may also be involved in the patho genesis of P carinii pneumonia. Both LTB4 and IL-8 may be involved in the recruitment of neutrophils and subsequent lung injury of NIP. Thes e data suggest that there are varying mechanisms by which inflammatory cells are recruited to the lung in different HIV-related lung disease s.