Am. J. Respir. Crit. Care Med., Volume 165, Number 8, April 2002, 1154-1160

Selective Cyclooxygenase-1 and -2 Inhibitors Each Increase Allergic Inflammation and Airway Hyperresponsiveness in Mice

R. Stokes Peebles Jr., Koichi Hashimoto, Jason D. Morrow, Ryszard Dworski, Robert D. Collins, Yuko Hashimoto, John W. Christman, Kyung-Ho Kang, Kasia Jarzecka, Jamye Furlong, Daphne B. Mitchell, Megha Talati, Barney S. Graham, and James R. Sheller

Department of Medicine and Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee; and Vaccine Research Center, National Institutes of Health, Bethesda, Maryland

Nonselective cyclooxygenase (COX) inhibition during allergic sensitization with ovalbumin in a murine model leads to an increase in the Type 2 cytokines interleukin-5 (IL-5) and IL-13; however, the effect of selective COX-1 and COX-2 inhibitors on these cytokines is unknown. We found that COX-1 protein was constitutively expressed in lung tissue. Expression of COX-1 protein did not increase with ovalbumin sensitization, but expression of COX-2 protein did. Ovalbumin-sensitized mice treated with either selective COX-1 inhibitor SC58560 (OVA-COX-1 inhibitor) or selective COX-2 inhibitor SC58236 (OVA-COX-2 inhibitor) had significantly greater airway hyperresponsiveness (p < 0.05) and higher levels of IL-13 (p < 0.05) in lung supernatants than did untreated mice that were ovalbumin sensitized (OVA). Lung mRNA levels for the chemokine receptors CCR1 through CCR5 (expressed on eosinophils, basophils, lymphocytes, and dendritic cells) were increased in the OVA-COX-2 inhibitor and OVA-indomethacin groups. We conclude that in the BALB/c mouse, COX inhibition with either a COX-1 or COX-2 inhibitor during allergen sensitization augments production of IL-13 and increases airway hyperresponsiveness.

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