Bleomycin-induced lung injury is enhanced by interferon-alpha

We have evaluated the effect of intraperitoneal (IF) injection of human recombinant interferon-2 alpha (IFN-alpha) on Bleomycin-induced pulmonary injury in hamsters. Pulmonary injury was induced by a single intratracheal (IT) instillation of Bleomycin (Bleo). Six groups of male Syrian hamsters were treated as follows: 1) IT Bleo and daily IP injections of low-dose interferon-alpha (2 x 10(4) U), 2) IT Bleo and daily IP injections of high-dose interferon-alpha (10(5) U), 3) IT Bleo and IP injections of saline, 4) LI saline and IP low-dose IFN-alpha, 5) IT saline and IP high-dose IFN-alpha, 6) IT saline and IP saline. Animals were sacrificed 28 days after IT treatment. Lung injury was evaluated histologically and biochemically. Treatment of hamsters with low-dose but not high-dose IFN-alpha significantly augmented the Bleo-induced lung injury, as determined by a semiquantitative morphological index. Lung hydroxyproline measurements were highest in Bleo-low-dose-IFN-alpha followed by Bleo-high-dose-IFN-alpha and Bleo-Sal as compared to Sal-Sal and Sal-IFN-alpha controls. These results suggest that IFN-alpha augments Bleo-induced lung injury but that this effect is complex and does not follow a simple-dose-response pattern. (C) 1997 Elsevier Science Inc.