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

TLDR

The study examined the role of COX‑2 in an in vivo inflammation model. Carrageenan injection into rat air pouches induced rapid inflammation with elevated prostaglandins and leukotrienes, and the authors measured COX‑2 mRNA and protein expression during this response. COX‑2 expression rose in tandem with prostaglandin production, localized to macrophages and lining cells, and selective COX‑2 inhibition (NS‑398) suppressed pouch inflammation without gastric ulceration, whereas nonselective indomethacin reduced both pouch and gastric prostaglandins and caused lesions, showing COX‑2 inhibitors are potent anti‑inflammatories lacking typical gastric side effects.

Abstract

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.