Xl. Chen et al., CD4(-LYMPHOCYTE MODULATION OF OZONE-INDUCED MURINE PULMONARY INFLAMMATION() T), American journal of respiratory cell and molecular biology, 12(4), 1995, pp. 396-403
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.