Conclusions
These data provide a new model for gammaherpesvirus exacerbation of established pulmonary fibrosis. The up-regulation of chemokines during viral infection and subsequent recruitment of fibrocytes to the lung likely contribute to augmentation of pulmonary fibrosis.
Methods
We used a model of fluorescein isothiocyanate-induced pulmonary fibrosis in mice. Infection with a murine gammaherpesvirus was given at time of established lung fibrosis. Measurements were made at the time of peak lytic viral replication. Measurements and main
Results
We demonstrate that infection with gammaherpesvirus can exacerbate established fluorescein isothiocyanate-induced fibrosis evidenced by increased total lung collagen, histologic changes of acute lung injury, and diminished lung function. Gammaherpesvirus can exacerbate preexisting fibrosis in a Th1 cytokine environment and in the absence of Th2 cytokines. Gammaherpesvirus increases fibrocyte recruitment to the lung in wild-type, but not CCR2(-/-) mice, in part because viral infection up-regulates production of CCL2 and CCL12, chemokines important for fibrocyte recruitment. In contrast, mouse adenovirus infection did not exacerbate collagen deposition. Conclusions: These data provide a new model for gammaherpesvirus exacerbation of established pulmonary fibrosis. The up-regulation of chemokines during viral infection and subsequent recruitment of fibrocytes to the lung likely contribute to augmentation of pulmonary fibrosis.