The role of cell-associated interleukin-1 in bleomycin-induced pulmonary fibrosis.

The activities of cell-associated IL-1 (IL-1 alpha) and extracellular IL-1 (IL-1 beta) in alveolar macrophages (AM) from rats with bleomycin-induced pulmonary fibrolosis were measured to determine their role in fibroblast growth. AM were obtained on Days 1, 3, 6, 9 and 12 after a intratracheal injection of bleomycin, and the IL-1 activity and fibroblast growth-stimulating activity in fixed AM and AM supernatants were measured. Higher cell-associated IL-1 activity was detected in AM from bleomycin-treated rats than in those of control on Day 1 through 9. But extracellular IL-1 activity in the supernatant of AM from bleomycin-treated rats significantly higher only on Day 1. Expression of IL-1 alpha mRNA in AM from bleomycin-treated rats was significantly higher than that in AM of control, but there was no significant difference in the mRNA levels of IL-1 beta in AM of these two groups. Fixed AM from bleomycin-treated rats caused growth-inhibition of fibroblasts in a density-dependent manner. The inhibitory activity was decreased by pretreatment of fixed AM with anti IL-1 alpha antibody, but not anti IL-1 beta antibody. These results suggest that cell-associated IL-1 (IL-1 alpha) is produced continuously in AM from rats with bleomycin-induced pulmonary fibrosis and may be important in regulation of this disorder by inhibiting fibroblast growth.