Modulation of bleomycin-induced pulmonary fibrosis in the BALB/c mouse by cyclophosphamide-sensitive T cells.
Endotracheal bleomycin treatment is an effective inducer of pneumonitis and pulmonary fibrosis. Certain strains of mice, however, develop only minimal or no pulmonary fibrosis after treatment with bleomycin. The mechanism of unresponsiveness or low responsiveness in the BALB/c strain of mice is examined in this article. Pretreatment with cyclophosphamide (100 mg/kg) 2 days prior to bleomycin instillation significantly augmented the fibrotic response in these mice. Treatment by cyclophosphamide alone at the same dosage caused no significant pulmonary disease or fibrosis. Furthermore, suppression of fibrosis in the cyclophosphamide-pretreated animals could be reconstituted with spleen cells from normal untreated donor mice. If the donor spleen cells were depleted of T cells by cytotoxic anti-Thy-1.2 antisera prior to infusion into recipient animals, no such reconstitution was observed, suggesting that a population of splenic T cells was responsible for the effect. Since this dose of cyclophosphamide is known to be cytotoxic for suppressor T cells, these data would signify that the intensity of the lung fibrogenic response to bleomycin in BALB/c mice can be modulated by a population of this T cell subset. Furthermore, the cell reconstitution data would exclude the possibility that cyclophosphamide augments the bleomycin response by non-T-cell-mediated synergistic effects on lung injury. Nevertheless, the results conclusively demonstrate the ability of T cells to modulate pulmonary fibrosis in vivo, at least in the BALB/c mouse.
D000818:Animals; D001761:Bleomycin; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011292:Premedication; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
D001761:Bleomycin; D003520:Cyclophosphamide