CD4(-LYMPHOCYTE MODULATION OF OZONE-INDUCED MURINE PULMONARY INFLAMMATION() T)

Inhalation of elevated levels of ozone produces a potent inflammatory response in the lung. The magnitude of this response to ozone exposure in mice is inbred strain dependent with the susceptible phenotype bei ng exemplified by the C57BL/6J (B6) strain and the resistant phenotype by the C3H/HeJ (C3) strain. To examine the role of T lymphocytes in t he regulation of ozone-induced pulmonary inflammation, mice were pretr eated by an intraperitoneal injection of anti-Thy1.2 monoclonal antibo dy (mAb), anti-CD4(+) mAb, or isotype-matched control antibodies (0.5 mg each) and subsequently exposed for 72 h to either filtered air or o zone (0.3 ppm). Immediately after ozone exposure, the cellular profile in the bronchoalveolar lavage fluids (BALF) was assessed. In isotype- treated controls of both strains of mice, ozone exposure induced signi ficant increases in the numbers of macrophages, neutrophils, lymphocyt es, and epithelial cells recovered in the BALF; however, the magnitude of each cell type recovered was significantly greater in B6 mice as c ompared with C3 mice. Both anti-Thy1.2 and anti-CD4(+) monoclonal anti body treatments decreased the number of each cell type recovered in th e B6 mice and increased the number of cells in the C3 mice. To determi ne if the CD4(+) T-cell-derived cytokine interleukin (IL)-4 was involv ed in the differential effect of T-cell depletion on the ozone-induced inflammatory responses of C3 and B6 mice, mice were pretreated with e ither 400 ng of recombinant mouse IL-4 or vehicle, or 5.0 mg anti-IL-4 receptor monoclonal antibody or an isotype-matched antibody before ei ther air or ozone exposure. Pretreatment of ozone-exposed C3 mice with anti-IL-4 receptor mAb significantly increased the numbers of cells r ecovered by bronchoalveolar lavage (BAL) although it had no effect on the magnitude of the cellular influx in B6 mice. IL-4 pretreatment of the B6 mice reduced the ozone-induced cellular influx although it had no effect on cellular influx in C3 mice. These results suggest that IL -4 inhibits ozone-induced pulmonary inflammatory responses. Moreover, the susceptibility of murine strains to ozone-induced inflammation may be due, in part, to genetic differences in the inducible production o f IL-4.