OXIDANT-ANTIOXIDANT IMBALANCE IN THE EXPERIMENTAL INTERSTITIAL LUNG-DISEASE INDUCED IN SHEEP BY VISNA-MAEDI VIRUS

Infection of sheep by visna-maedi virus causes an interstitial pneumon itis similar to that associated with human immunodeficiency virus type -1 (HIV-1). Visna-maedi virus infection of alveolar macrophages leads to their activation. In this study we determined whether an imbalance in oxidant-antioxidant activity may be involved in the pathogenesis of the disease. We investigated the spontaneous and phorbol myristate ac etate (PMA)-induced release of hydrogen peroxide (H2O2), and the activ ities of superoxide dismutase and glutathione peroxidase in alveolar m acrophages from lambs experimentally-infected with visna-maedi virus, and in ovine alveolar macrophages infected in vitro. Alveolar macropha ges from lambs experimentally-infected in vivo exhibited normal sponta neous H2O2 release and had superoxide dismutase and glutathione peroxi dase activities similar to those from control animals. In contrast, af ter in vitro stimulation with PMA the H2O2 production by macrophages f rom experimentally-infected lambs was significantly increased, Similar ly, spontaneous and PMA-induced H2O2 production by in vitro infected m acrophages was significantly increased as compared to controls. In con clusion, the increased capacity of alveolar macrophages infected with the human immunodeficiency virus type-1-related visna-maedi virus to r elease hydrogen peroxide on stimulation suggests an oxidant-antioxidan t imbalance, which may contribute to the pathogenesis of the observed chronic interstitial pneumonitis.