Type I interleukin-1 receptor is required for pulmonary responses to subacute ozone exposure in mice

Interleukin (IL)-1, a proinflammatory cytokine, is expressed in the lung after ozone (O-3) exposure. IL-1 mediates its effects through the type I IL-1 receptor(IL-1 RI), the only signaling receptor for both IL-1 alpha and ILA P. The purpose of this study was to determine the role of IL-1 RI in pulmonary responses to O-3. To that end, wild-type, C57BL/6 (IL-1 RI+/+) mice and IL-1 RI-deficient (IL-1 RI-/-) mice were exposed to O-3 either subacutely (0.3 ppm for 72 h) or acutely (2 ppm for 3 h). Subacute O-3 exposure increased bronchoalveolar lavage fluid (BALF) protein, interferon-gamma-inducible protein (IP)-10, soluble tumor necrosis factor receptor 1 (sTNFR1), and neutrophils in IL-1RI(+/+) and IL-1 RI-/- mice. With the exception of IP-10, all outcome indicators were reduced in IL-1RI(-/-) mice. Furthermore, subacute 03 exposure increased IL-6 mRNA expression in IL-1RI(+/+), but not IL-1RI(-/-) mice. Acute (2 ppm) 03 exposure increased BALF protein, IL-6, eotaxin, KC, macrophage inflammatory protein (MIP)-2, IP-10, monocyte chemotactic protein-1, sTNFR1, neutrophils, and epithelial cells in IL-1RI(+/+) and IL-1RI(-/-) mice. For IL-6, eotaxin, MIP-2, and sTNFR1, there were small but significant reductions of these outcome indicators in IL-1 Rl(-/-) versus IL-1 RI+/+ mice at 6 hours after exposure, but not at other time points, whereas other outcome indicators were unaffected by IL-11 RI deficiency. These results suggest that IL-1RI is required for O-3-induced pulmonary inflammation during subacute O-3 exposure, but plays a more minor role during acute O-3 exposure. in addition, these results suggest that the induction of IL-6 via IL-1RI may be important in mediating the effects of O-3 during subacute exposure.