Purpose: To determine the contribution of intra-alveolar cells as opposed to cells fixed in the interstitium in the development of radiation-induced lung injury.
Materials and methods: C3H/HeN mice were irradiated to the thorax with various doses of radiation. The cellular composition and cytokine production were assessed in the two sites by histological staining and RNase protection assay.
Results: Following thoracic irradiation, there was an initial decrease in the number of bronchial alveolar lavage (BAL) cells that was followed after 2 months by a dose-dependent increase up to 4 months. Foamy Mac-1 positive macrophages were present early in the BAL populations, which also expressed the pro-inflammatory cytokines TNF-alpha, IL-1alpha and IL-1beta, but this response subsided by the time of onset of pneumonitis (3 months). In contrast, in whole lung tissue there was a steady increase in Mac-1 positive cells and increased expression of TNF-alpha, IL-1alpha and IL-1beta mRNAs to maximum levels at 3-4 months.
Conclusions: These data indicate distinct temporal and spatial changes in pro-inflammatory cytokine gene expression in different cellular compartments of the irradiated lung. BAL cells became inflammatory early on, but interstitial cells became involved later and were probably more involved in contributing to the pneumonitis.