| Bronchiolitis Obliterans Organizing Pneumonia (BOOP) and Acute Respiratory Distress Syndrome (ARDS) are two pulmonary diseases with fibrotic components. BOOP is characterized by the development of fibrosis in the alveolar spaces of the lung and is often of unknown etiology but has been associated with pulmonary damage due to viral infections, environmental toxins, or lung and bone marrow transplants. ARDS is described by two phases, an acute phase and a fibrotic phase. The initial acute phase of ARDS is characterized by a cellular infiltration accompanied by edema, hemorrhage, and the formation of hyaline membranes. Patients that survive the acute phase of ARDS typically develop fibrosis found either in the interstitium or the alveoli of the lung. ARDS has been associated with lung injury due to bacterial infections, viral infections, sepsis, shock, severe trauma, and near-drowning.; Our laboratory has established models of BOOP and ARDS in CBA/J mice. Infection with 1 × 106 PFU reovirus 1/L (BOOP) results in a cellular infiltration characterized predominantly by T lymphocytes. Following this cellular infiltration is fibrosis localized to the lung alveoli. Several key cytokines and chemokines produced in the lung post infection are IFN-γ, MCP-1, and IL-6 which have been implicated in T cell activity and have profibrotic activity. In contrast, mice infected with 1 × 107 PFU reovirus 1/L (ARDS) develop a cellular infiltrate mainly comprised of neutrophils and macrophages. Accompanying this cellular infiltration are pulmonary edema, hemorrhage, and the formation of hyaline membranes. Mice that survive this acute phase of ARDS, develop pulmonary fibrosis histologically similar to BOOP. Several key cytokines and chemokines produced in the lung post reovirus 1/L infection include IFN-γ, MCP-1, MIP-1α, and MIP-2. Because differences exist in the cellular profiles and the cytokine and chemokine profiles of mice that develop BOOP versus those that develop ARDS, the role of T lymphocytes in the development of fibrosis was evaluated in each model.; A differential role for T cells was observed in the development of fibrosis associated with BOOP versus ARDS. Neonatally thymectomized (nTx) CBA/J mice, which are T cell deficient, as well as CBA/J mice treated with methylprednisolone (MPS) did not develop BOOP fibrotic lesions post reovirus 1/L infection. In both cases, a severe depression in cytokine and chemokine expression was observed including the depressed expression of IFN-γ and MCP-1. In contrast, nTx CBA/J mice as well as CBA/J mice treated with MPS still developed ARDS and the fibrosis associated with late ARDS. These results suggest that T lymphocytes and the cytokines associated with their activity are essential to the development of fibrosis associated with BOOP but not the fibrosis associated with ARDS. Furthermore, the expression of IFN-γ and MCP-1 may be necessary prior to the development of fibrosis and promote the development of fibrosis in CBA/J mice post infection with reovirus 1/L.; Therefore, although the administration of reovirus 1/L results in the development of BOOP and ARDS in CBA/J mice, different cellular and molecular mediators are important to the development of fibrosis associated with these diseases. Therefore, in order to effectively prevent and/or treat these diseases, the underlying mechanisms important in the pathogenesis of the disease must be evaluated. |
