COMPARTMENTALIZED IL-8 AND ELASTASE RELEASE WITHIN THE HUMAN LUNG IN UNILATERAL PNEUMONIA

Because interleukin 8 (IL-8) is a potent neutrophil chemotactic and ac tivating cytokine, we investigated IL-8 production in relation to neut rophil migration and elastase release in the human lung during unilate ral community-acquired pneumonia (CAP). In 17 patients, the local resp onse in the involved lung was compared with that in the contralateral, noninvolved lung, and with the systemic response. Eight healthy volun teers served as controls. IL-8, total neutrophil elastase (NE), free e lastase activity, alpha(1)-antitrypsin (alpha(1)-AT), and total leukoc yte and neutrophil counts were evaluated in bronchoalveolar lavage flu ids (BALF). Mean IL-8 concentrations in BALF from the involved lungs o f the patients were significantly greater than those in BALF from the noninvolved lung or from controls (p less than or equal to 0.001). By contrast, the serum IL-8 concentration was not different in patients a nd in controls. Total NE and alpha(1)-AT concentrations were increased in BALF from the involved lung as compared with the noninvolved lung or controls (p less than or equal to 0.001). The elastase-inhibitory c apacity of alpha(1)-AT in BALF was impaired in the involved lung of se ven of the 14 patients as compared with the controls, leading to free elastase activity in the involved lung of all patients with CAP. Plasm a total NE concentrations were significantly greater in the CAP patien ts than in the controls. IL-8 concentrations in BALF correlated positi vely with total leukocyte counts, absolute numbers and percentages of neutrophils, total NE concentrations, and free elastase activity. Our results suggest that during unilateral CAP, locally produced IL-8 may trigger neutrophil accumulation and activation, thus contributing to a local elastase/antielastase imbalance within the site of infection.