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Early changes in rectal nitric oxide and mucosal inflammatory mediators in Crohn's colitis in response to infliximab
T Ljung1, L-G Axelsson, M Herulf
1Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden. Per.Hellstrom@ki.se
Background:
Treatment with tumor necrosis factor-alpha 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-alpha, interleukin-1beta and interferon-gamma 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-alpha, interleukin-1beta and interferon-gamma and may serve as a quantitative biomarker of intestinal inflammation.
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