Intrapulmonary interleukin 1 mediates acute immune complex alveolitis in the rat

Abstract

Interleukin 1[alpha] and [beta] are polypeptide cytokines that possesses a wide variety of immunologic and inflammatory 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 12-fold increase in bronchoalveolar lavage fluid interleukin 1 activity. Intratracheal instillation of neutralizing anti-interleukin 1[beta] 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. Morphometric analysis and measurements of myeloperoxidase activities in whole lung homogenates from rats that received anti-interleukin 1[beta] 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.