EARLY AND PERSISTENT ALTERATIONS IN THE EXPRESSION OF INTERLEUKIN-1-ALPHA, INTERLEUKIN-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA MESSENGER-RNALEVELS IN FIBROSIS-RESISTANT AND SENSITIVE MICE AFTER THORACIC IRRADIATION

Fibrosis, characterized by the accumulation of collagen, is a conseque nce of a chronic inflammatory response. The purpose of this study was to determine if tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta mRNA expression are altered acutely after irradiation, during the so-called ''latent'' phase of pulmonary injury, and to examine if these alterations persist through the develo pment of pneumonitis and fibrosis. Further, we wished to determine if these changes differ between two strains of mice which vary in their s ensitivity to radiation. Fibrosis-sensitive (C57BL/6) and fibrosis-res istant (C3H/HeJ) mice were irradiated with a single dose of 5 or 12.5 Gy to the thorax. Total lung RNA was prepared and immobilized by slot blotting and hybridized with radiolabeled cDNA probes encoding for TNF -alpha, IL-1 alpha and IL-1 beta. Autoradiographic data were quantifie d by video densitometry and results normalized to a control probe enco ding for glyceraldehyde-3-phosphate dehydrogenase. It was found that T NF-alpha mRNA levels were increased in C57BL/6 mice at days 1 and 7 po stirradiation after 5 Gy and day 14 postirradiation after both 5 and 1 2.5 Gy, and IL-1 alpha mRNA levels were increased in C57BL/6 mice at d ays 56, 112 and 182 postirradiation after both 5 and 12.5 Gy, and IL-1 beta mRNA levels in the C3H/HeJ mice were increased at days 56 and 18 2 postirradiation after 12.5 Gy. In summary, these studies demonstrate d early and persistent alterations in TNF-alpha, IL-1 alpha and IL-1 b eta mRNA levels even at the lower dose (5 Gy). The temporal relationsh ip between the elevation of these cytokines and the strain-dependent v ariation in fibrosis response suggests that IL-1 alpha and TNF-alpha c ontribute to the radiation-induced component of pulmonary fibrosis, wh ereas IL-1 beta may have a protective function. (C) 1996 by Radiation Research Society