PULMONARY CHANGES INDUCED BY COMBINED MOUSE INTERFERON-BETA (RMUIFN-BETA) AND IRRADIATION IN NORMAL MICE - TOXIC VERSUS PROTECTIVE EFFECTS

This study in normal mice was undertaken to investigate possible enhan cement of pulmonary toxicity by interferon - beta (IFN-beta) combined with single doses of irradiation. A pharmacokinetic study preceded the toxicity study to determine the optimal route and timing of IFN admin istration. Graded single doses of radiation were combined with graded doses of IFN. Pulmonary toxicity was determined using endpoints of alv eolar surfactant and procollagen in lung lavage fluid at 7 days, breat hing frequency, lethality and histology. Increased lethality was seen when IFN was combined with irradiation at 12.5 Gy vs. irradiation alon e. This occurred between 20 and 30 weeks post treatment with no increa sed breathing frequency or surfactant release, suggesting independent mechanisms of injury. Increased breathing frequency after 40 weeks, us ually associated with fibrosis, was less pronounced for IFN treated vs . irradiation only controls. Ultrastructural studies at 72 weeks sugge st reduced fibrosis in lungs of IFN treated vs. irradiation only contr ols. Supporting this was the finding that Procollagen III, a biosynthe tic precursor of collagen, was increased in the lavage fluid at 7 days for all radiation doses but decreased with the addition of IFN at 12. 5 and 15 Gy. Interferons can act either as sensitizers or radioprotect ors, depending on the biological system and type of interferon. Our st udy suggests that while IFN-beta may increase the acute effects of rad iation in the mouse lung, some protection from radiation-induced fibro sis, possibly related to alteration of immune mechanisms, may exist.