Published ahead of print on June 15, 2007, doi:10.1165/rcmb.2006-0315OC
© 2007 American Thoracic Society DOI: 10.1165/rcmb.2006-0315OC Type I Interleukin-1 Receptor Is Required for Pulmonary Responses to Subacute Ozone Exposure in MiceMolecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts Correspondence and requests for reprints should be addressed to Richard A. Johnston, Ph.D., Room 8.104A, Medical Research Building, Division of Allergy, Pulmonary, Immunology, Critical Care, and Sleep, Department of Internal Medicine, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1083. E-mail: rajohnst{at}utmb.edu
Interleukin (IL)-1, a proinflammatory cytokine, is expressed in the lung after ozone (O3) exposure. IL-1 mediates its effects through the type I IL-1 receptor (IL-1RI), the only signaling receptor for both IL-1
Key Words: bronchoalveolar lavage • interleukin-6 • macrophage • neutrophil • soluble tumor necrosis factor receptor
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and IL-1
. The purpose of this study was to determine the role of IL-1RI in pulmonary responses to O3. To that end, wild-type, C57BL/6 (IL-1RI+/+) mice and IL-1RI–deficient (IL-1RI–/–) mice were exposed to O3 either subacutely (0.3 ppm for 72 h) or acutely (2 ppm for 3 h). Subacute O3 exposure increased bronchoalveolar lavage fluid (BALF) protein, interferon-
–inducible protein (IP)-10, soluble tumor necrosis factor receptor 1 (sTNFR1), and neutrophils in IL-1RI+/+ and IL-1RI–/– mice. With the exception of IP-10, all outcome indicators were reduced in IL-1RI–/– mice. Furthermore, subacute O3 exposure increased IL-6 mRNA expression in IL-1RI+/+, but not IL-1RI–/– mice. Acute (2 ppm) O3 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-1RI–/– versus IL-1RI+/+ mice at 6 hours after exposure, but not at other time points, whereas other outcome indicators were unaffected by IL-1RI deficiency. These results suggest that IL-1RI is required for O3-induced pulmonary inflammation during subacute O3 exposure, but plays a more minor role during acute O3 exposure. In addition, these results suggest that the induction of IL-6 via IL-1RI may be important in mediating the effects of O3 during subacute exposure. 
