RADIATION-INDUCED LUNG INJURY IN-VIVO - EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA PRECEDES FIBROSIS

Cytokine release from irradiated cells has been postulated to start so on after irradiation preceding detectable clinical and pathological ma nifestation of lung injury. The expression of transforming growth fact or beta (TGF beta), a fibrogenic and radiation-inducible cytokine, was studied from 1-16 weeks after the 15 and 30 Gray (Gy) of thoracic irr adiation to rats. Thoracic irradiation caused an increase in TGF beta protein in bronchoalveolar lavage (BAL) fluid peaking at 3-6 weeks as compared to sham-irradiated control rats. Steady state TGF beta mRNA e xpression as shown by whole lung northern blot assay paralleled the TG F beta protein expression in BAL fluid. The peak of TGF beta protein i ncrease in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8-10 weeks after irradiation. In conclusion, TGF beta and mRNA and protein upreg ulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.