Cyclo-oxygenase-2 overexpression has been described in experimental
colitis. However, there are controversial findings suggesting that its inhibition by selective cyclo-oxygenase-2 inhibitors not only may have a beneficial effect on experimental
colitis, but also exacerbate the
inflammation-associated colonic injury. Thus, the role of cyclo-oxygenase-2 inhibitors in the possible modulation of colon
inflammation is controversial and remains uncertain. In this study, we evaluated the effects of the selective cyclo-oxygenase-2 inhibitor,
rofecoxib, on the extent and severity of
ulcerative colitis caused by intracolonic administration of
2,4,6-trinitrobenzene sulphonic
acid (TNBS) in rats. The lesions and the inflammatory response were assessed by histology and measurement of
myeloperoxidase activity.
Interleukin-1 beta,
prostaglandin E(2) and D(2) levels in colon mucosa and the immunohistochemical expression of the cyclo-oxygenases-1 and -2 were also studied. Finally, we investigated the effects of
rofecoxib on apoptosis of colonocytes by the appearance of DNA fragmentation.
Inflammation following TNBS was characterized by increased colonic wall thickness, oedema, diffuse inflammatory cell infiltration in the mucosa, and
necrosis. Increased
myeloperoxidase activity, as an index of neutrophil infiltration in the mucosa, and
interleukin-1 beta levels were also measured in the colon. Administration of
rofecoxib significantly (P<0.05) reduced the colonic damage, the degree of neutrophil infiltration, and
interleukin-1 beta levels. In addition, apoptosis was significantly increased in TNBS-treated rats, but not in
rofecoxib plus TNBS-treated rats. We concluded that
rofecoxib seems to have beneficial effects in TNBS-induced
colitis by diminishing the initial stage of
inflammation, probably by a mechanism related to inhibition of
prostaglandin E(2) by the cyclo-oxygenase-2 pathway. The data suggest that cyclo-oxygenase-2-selective inhibitors may have a therapeutic role in
ulcerative colitis.