Viral infection modulates expression of hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is a granulomatous, inflammatory lung dis ease caused by inhalation of organic Ags, most commonly thermophilic actino mycetes that cause farmer's lung disease. The early response to Ag is an in crease in neutrophils in the lung, whereas the late response is a typical T h1-type granulomatous disease. Many patients who develop disease report a r ecent viral respiratory infection, These studies were undertaken to determi ne whether viruses can augment the inflammatory responses in HP, C57BL/6 mi ce were exposed to the thermophilic bacteria Saccharopolyspora rectivirgula (SR) for 3 consecutive days per wk for 3 wk. Some mice were exposed to SR at 2 wk after infection with respiratory syncytial virus (RSV), whereas oth ers were exposed to SR after exposure to saline alone or to heat-inactivate d RSV, SR-treated mice developed a typical, early neutrophil response and a late granulomatous inflammatory response, Up-regulation of IFN-gamma and I L-2 gene expression was also found during the late response. These response s were augmented by recent RSV infection but not by heat-inactivated RSV, M ice with a previous RSV infection also had a greater early neutrophil respo nse to SR, with increased macrophage inflammatory protein-2 (MIP-2, murine equivalent of IL-8) release in bronchoalveolar lavage fluid. These studies suggest that viral infection can augment both the early and late inflammato ry responses in HP.