Effects of octreotide treatment on early TNF‐α production and localization in experimental chronic colitis

Background : Colitis induced by trinitrobenzene sulphonic acid (TNB) is a model of Th1 disease, mainly explored from the third day of induction. It has recently been shown that octreotide and other somatostatin analogues can modify inflammatory/immune processes by acting on cytokines. Aim : To examine TNFα production and the effect of preventive treatment with octreotide, during the early phase of TNB‐colitis. Methods : Thirty milligrams TNB with 50% ethanol was instilled into the colon of male Wistar rats. Treated groups received octreotide (2 × 10 μg.day/rat) or dexamethasone (1 × 2 mg.day/kg), subcutaneously, with the first injection before TNB. Eight and 80 h later, the colon was excised and processed for histology, TNFα immunohistochemistry, quantification of cytokine release ex vivo and tissue‐inducible NO synthase (iNOS) activity. Results : Maximal TNFα production was observed at the 8th hour, associated with intense immunostaining of the external muscle layer. Octreotide treatment decreased TNFα expression (staining and activity) and iNOS activity. At the 80th hour, submucosal macrophages were positive for TNFα and colonic production of IL1β and interferon γ was increased; all these effects were reduced by octreotide treatment. Conclusions : TNFα was expressed early by resident muscle cells, before staining of infiltrated immune cells and increased production of interferon γ. TNFα regulation by octreotide suggests that this drug might exert anti‐inflammatory properties via smooth muscle cells.