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.