PULMONARY MECHANICAL AND IMMUNOLOGICAL DYSFUNCTION IN A MURINE MODEL OF AIDS

Human immunodeficiency virus-infected patients occasionally exhibit al veolar septal wall thickening and decreases in gas diffusion capacity, but the mechanism underlying these abnormalities is unknown. The pres ent study evaluated septal wall thickness and gas exchange properties in a murine model of the acquired immunodeficiency syndrome and determ ined whether there were alterations in lung lymphocyte deposition and activation that could contribute to changes in respiratory structure a nd function. Although alveolar septal wall thickness did not differ fr om control at 1, 2, and 4 wk postimmunosuppressive virus infection, at 8 wk after infection, septal wall thickness was substantially increas ed. Immunohistochemical evaluation at this time revealed marked increa ses in the septal wall deposition of fibronectin and collagen type IV. Pulmonary function tests on anesthetized mice with virus-induced sept al wall thickening demonstrated that, although total lung capacity, co mpliance, and functional residual capacity were unaltered, diffusion c apacity for carbon monoxide was significantly impaired. A diffuse nons pecific interstitial pneumonitis was present in lungs of immunodeficie nt mice, and flow cytometry indicated that both lymphocytes and macrop hages were activated. Reverse transcriptase-polymerase chain reaction analysis of lung lymphocytes demonstrated enhanced mRNA expression for several cytokines known to affect lung structure. These results show that impaired gas exchange occurs in a murine model of acquired immuno deficiency syndrome and suggest that such alterations may be mediated by elaboration of cytokines from activated lung lymphocytes and macrop hages.