Intrapulmonary interleukin 1 mediates acute immune complex alveolitis in the rat

Interleukin la and p are polypeptide cytokines that possesses a wide variety of immunologic and intlammatory activities. We have examined the role of intrapulmonary interleukin 1 in the pathogenesis of acute IgG immune complex alveolitis in the rat. Intratracheal instillation of IgG anti-bovine serum albumin accompanied by intravenous infusion of bovine albumin results in acute neutrophil and complement-dependent alveolitis. Over the course of evolving lung injury there was a 1Zfold increase in bronchoalveolar lavage fluid interleukin 1 activity. Intratracheal instillation of neutralizing anti-interleukin lp antibodies upon induction of lung injury resulted in a dose-dependent reduction in lung injury as assessed by measurements of pulmonary hemorrhage and vascular permeability. Morphomenic analysis and measurements of myeloperoxidase activities in whole lung homogenates from rats that received anti-interleukin 10 revealed a pronounced reduction in neutrophil recruitment compared to positive controls. Incubation of isolated alveolar macrophages with preformed IgG immune complexes resulted in dose-dependent interleukin 1 secretion. These data suggest that intrapulmonary IL-1 activity plays a role in neutrophil recruitment and is necessary for the full development of acute IgG immune complex induced lung injury in the rat. 0 1991 Academi