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Early changes in rectal nitric oxide and mucosal inflammatory mediators in Crohn’s colitis in response to infliximab treatment
Author(s) -
LJUNG T.,
AXELSSON L.G.,
HERULF M.,
LUNDBERG J. O.,
HELLSTRÖM P. M.
Publication year - 2007
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2007.03284.x
Subject(s) - infliximab , medicine , nitric oxide , nitric oxide synthase , gastroenterology , tumor necrosis factor alpha , cytokine , inflammatory bowel disease , crohn's disease , immunohistochemistry , inflammation , colitis , immunology , pathology , disease
SUMMARY Background Treatment with tumor necrosis factor‐α monoclonal antibody (infliximab) reduces clinical activity and intestinal inflammation in Crohn’s disease. Aim To study the time‐course of the effects of infliximab with reference to mucosal cytokine and inducible nitric oxide synthase expression. Methods Thirty‐two patients with Crohn’s disease were treated with single dose infliximab (5 mg/kg). Disease activity was assessed days 1, 3, 7 and 28 using Harvey–Bradshaw index. Rectal nitric oxide levels were determined and rectal biopsies collected before treatment, 1 h after infusion and on days 3, 7 and 28. Immunohistochemical staining against inducible nitric oxide synthase, tumor necrosis factor‐α, interleukin‐1β and interferon‐γ were performed. Results Clinical response was seen in 14 patients with down‐regulation of global immunohistochemistry expression, reaching nadir day 3. Rectal nitric oxide was increased at baseline (3578 ± 1199 parts per billion, ppb) compared with controls (89 ± 13 ppb) ( P < 0.001). In patients with clinical response, rectal nitric oxide decreased from 3926 ± 1687 ppb to 1050 ± 428 ppb day 28 ( P < 0.05). Conclusions Down‐regulation of mucosal inflammatory mediators occurs after infliximab. Rectal nitric oxide levels parallel down‐regulation of inducible nitric oxide synthase, tumor necrosis factor‐α, interleukin‐1β and interferon‐γ and may serve as a quantitative biomarker of intestinal inflammation.