Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic

Jaime L. Masferrer, Ben S. Zweifel, Pamela T. Manning, Scott D. Hauser, Kathleen M. Leahy, Walter G. Smith, Peter C. Isakson, Karen Seibert

Research output: Contribution to journalArticlepeer-review

1310 Scopus citations


We have examined the role of cyclooxygenase 2 (COX-2) in a model of inflammation in vivo. Carrageenan administration to the subcutaneous rat air pouch induces a rapid inflammatory response characterized by high levels of prostaglandins (PGs) and leukotrienes in the fluid exudate. The time course of the induction of COX-2 mRNA and protein coincided with the production of PGs in the pouch tissue and cellular infiltrate. Carrageenan-induced COX-2 immunoreactivity was localized to macrophages obtained from the fluid exudate as well as to the inner surface layer of cells within the pouch lining. Dexamethasone inhibited both COX-2 expression and PG synthesis in the fluid exudate but failed to inhibit PG synthesis in the stomach. Furthermore, NS- 398, a selective COX-2 inhibitor, and indomethacin, a nonselective COX- 1/COX-2 inhibitor, blocked proinflammatory PG synthesis in the air pouch. In contrast, only indomethacin blocked gastric PG and, additionally, produced gastric lesions. These results suggest that inhibitors of COX-2 are potent antiinflammatory agents which do not produce the typical side effects (e.g., gastric ulcers) associated with the nonselective, COX-1-directed antiinflammatory drugs.

Original languageEnglish
Pages (from-to)3228-3232
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Apr 12 1994


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