Effect of whole-body x-irradiation on antigen-induced airway response in sensitized guinea pigs.

Abstract

The objectives of this study were to test the hypothesis that x-irradiation inhibits the late asthmatic response (LAR) without influencing the early asthmatic response (EAR) and to examine the mechanism of the inhibitory effect. Twenty sensitized guinea pigs were irradiated at a dose of 8 Gy. The next day, one-half of the animals were injected intravenously with spleen cells (2 x 10(8)) collected from unirradiated sensitized guinea pigs, whilst the other half were injected with vehicle only. Ten additional unirradiated sensitized guinea pigs also received vehicle only. Antigen inhalation challenge took place two days later. Pulmonary resistance was measured for 6 h after antigen exposure, and bronchoalveolar lavage and lung fixation were then undertaken. The area under the percentage pulmonary resistance curve 2-6 h after allergen inhalation was used for analysis of the LAR, while the maximal percentage change in pulmonary resistance was used for analysis of the EAR. Irradiation abolished the LAR (364.4+/-49.4 versus 62.8+/-10.4) without inhibiting the EAR (229.3+/-27.2 versus 278.7+/-40.2) and significantly inhibited the accumulation of eosinophils and lymphocytes in the airways. Transfer of spleen cells restored the LAR (334.4+/-66.8) and the recruitment of cells to the levels seen in unirradiated sensitized guinea pigs. In addition, transfer of only CD4+ T-lymphocytes separated from the spleen cells restored the LAR (439.4+/-62.1) and the cell infiltration into the airways. These inhibitory effects of x-irradiation were due to decreases in numbers of CD4+ T-lymphocytes.