Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice

(Background & Aims) under bar: Chronic abdominal symptoms develop in some p atients after acute enteric infection, This study examined mechanisms under lying smooth muscle hypercontractility that persists after acute infection in mice, (Methods) under bar: Euthymic and athymic National Institutes of H ealth (NIH) Swiss mice were infected with Trichinella spiralis and studied 4 weeks postinfection (PI), Isometric tension was assessed in longitudinal muscle, Cytokine and cyclooxygenase (COX)-2 messenger RNA was determined in the muscularis externa by reverse-transcription polymerase chain reaction. COX-2 protein was identified by immunohistochemistry and prostaglandin E-2 was measured by enzymatic immunoassay. Studies were performed in euthymic and athymic NIH Swiss mice 28 days PI and in the presence or absence of tre atment with corticosteroid or COX inhibitors. (Results) under bar: Muscle h ypercontractility was evident in euthymic mice but was attenuated in athymi c mice or in steroid-treated euthymic mice 28 days PI, Expression of Th2 cy tokines interleukins 4, 5, and 13 was increased during the acute infection but not thereafter, COX-2 was localized to muscle and its enzymatic activit y remained significantly increased in the muscle on day 28 PI, Selective CO X-2 inhibition in vitro reduced the sustained increase in tension generatio n. (Conclusions) under bar: These findings show that COX-2 activation in re sident cells of the muscularis externa contributes to the muscle hypercontr actility that persists after infection.