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

JL Masferrer, BS Zweifel, PT Manning… - Proceedings of the …, 1994 - National Acad Sciences
JL Masferrer, BS Zweifel, PT Manning, SD Hauser, KM Leahy, WG Smith, PC Isakson…
Proceedings of the National Academy of Sciences, 1994National Acad Sciences
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 …
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.
National Acad Sciences