Exacerbation of bleomycin-induced lung injury in mice by amifostine

Bleomycin (BLM) induces lung injury and fibrosis in the murine lung and enh ances tumor necrosis factor (TNF)-alpha and collagen mRNA expression in the murine lung. Amifostine is a cytoprotective agent that protects normal tis sues from the cytotoxic effects of chemo- and radiation therapy. We investi gated the effect of amifostine in BLM-induced lung injury in mice. Mice rec eived intraperitoneal amifostine (200 mg/kg) 30 min before and/or 1, 3, and 7 days after an intratracheal injection of saline or BLM (4 U/kg). The ani mals were killed 14 days after BLM exposure, and their lungs were studied f or TNF-alpha and collagen mRNA expression, hydroxyproline content, and hist opathology. Light microscopy demonstrated that amifostine exacerbated the B LM-induced lung injury in mice. Increased TNF-alpha mRNA expression as a re sult of BLM exposure was not modulated by amifostine treatment. In contrast , amifostine treatment enhanced the BLM-induced expression of alpha(1)(I) p rocollagen mRNA in the lung. Similarly, mice treated with amifostine before BLM exposure accumulated significantly higher amounts of hydroxyproline (1 11 +/- 5 mu g/lung) than BLM-treated animals (90 +/- 6 mu g/lung). These da ta suggest that amifostine treatment exacerbates BLM-induced lung injury in mice.