Celecoxib inhibits early cutaneous wound healing

Abstract

BACKGROUND: Cyclooxygenase-2 (COX-2) is an inducible enzyme that is rapidly upregulated in response to injury, resulting in the production of prostaglandin E2 (PGE2), a primary mediator of inflammation and wound healing. The selective COX-2 inhibitor, celecoxib, is was used to treat pain and inflammation. When used to treat injuries, we postulated that loss of PGE2 activity by COX-2 inhibition would have detrimental effects on wound healing. Our objective was to study the effect of selective COX-2 inhibition with celecoxib on cutaneous wound healing.

MATERIALS AND METHODS: C57BL/6J mice with uniform full-thickness wounds (1 cm(2)) to their dorsum were fed diet with or without celecoxib (1500 ppm). Wound closure analysis measured wound contraction, reepithelialization, and open wound as a percentage of the initial wound area, and was quantified by planimetry. Wounds were excised en bloc at day 7 to examine cellular proliferation, angiogenesis, cytokine production, and extracellular matrix (ECM) formation.

RESULTS: Celecoxib-induced reduction in wound PGE2 levels was documented by enzyme-linked immunosorbent assay on day 7 after wounding. Wound contraction and reepithelialization were significantly reduced by celecoxib treatment, resulting in a 20% greater open wound area at day 7 (P < 0.05). In response to celecoxib treatment, immunohistochemistry analysis showed epithelial cell proliferation, angiogenesis, and ECM components including collagen and myofibroblasts were significantly decreased.

CONCLUSIONS: Wound healing is significantly delayed by celecoxib treatment. These data indicate that COX-2 and its downstream product PGE2 modulate the activity of multiple essential functions of the inflammatory stroma, including epithelial proliferation, angiogenesis, and ECM production. As a result, reepithelialization and wound closure are delayed by celecoxib treatment. These findings have potential clinical implications in postoperative wound management.