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Objective: To evaluate the effect of Ridogrel enemas (Janssen Research Foundation, Beerse, Belgium) on disease activity and mucosal inflammatory mediators in patients with active left-sided ulcerative colitis., Design and Methods: Eleven patients with active left-sided ulcerative colitis were evaluated in an open non-placebo-controlled pilot study. All patients were treated with Ridogrel enemas (300 mg/40 ml once daily) over four weeks. A disease activity score based on clinical, endoscopic and histological criteria was obtained before and after treatment with Ridogrel. The concentrations of thromboxane B2 (TxB2), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were measured in mucosal biopsies before and after treatment., Results: One patient discontinued treatment because of progression of disease, the other ten patients tolerated the Ridogrel enemas well. Mucosal TxB2 concentration decreased significantly in all patients. The mucosal concentrations of the other inflammatory mediators (PGE2, IL-6 and TNF-alpha) were unaltered. The disease score decreased in five patients. However, clinical improvement was not always associated with a decrease in endoscopic and/or histological scores., Conclusions: This pilot study shows that Ridogrel enemas selectively reduce mucosal TxB2 concentration.

Objective: Ulcerative colitis (UC) is predominantly a disease of non-smokers and treatment with transdermal nicotine improves symptoms in UC patients, whereas smoking seems to have a deleterious effect in patients with Crohn's disease (CD). In CD the cytokine profile is of a dominant TH1 (T helper 1) pattern whereas in UC the TH2 pattern predominates. To find an explanation for the beneficial effect of nicotine in UC and the deteriorative effect in CD we studied the in-vivo effect of nicotine on the interleukin 2 (IL-2), IL-10 and tumour necrosis factor alpha (TNF alpha) production by human cells., Design: Eleven healthy male non-smokers were included in this study. The volunteers applied nicotine patches with a regulated release of 5 mg (day 1 and 2), 10 mg (day 3 and 4) and 15 mg (day 5, 6 and 7) nicotine per day., Methods: Heart rate and blood pressure were recorded, nicotine and cotinine concentrations in plasma measured before and after 2, 4 and 7 days of treatment. Non-adherent mononuclear cells (NAC) were isolated from peripheral blood obtained from the subjects before and after 7 days of treatment. The NAC were cultured in the absence or presence of phytohemagglutinin for 48 h. Total amount of IL-2, IL-10 and TNF alpha formed were measured in the supernatants using specific ELISAs., Results: Treatment with nicotine caused a significant inhibition of IL-10 production by NAC. In contrast, nicotine patch treatment had no effect on the production of IL-2 and TNF alpha., Conclusions: Nicotine in vivo has an inhibitory effect on TH2 cell function as measured by inhibition of IL-10 production, but does not appear to have any effect on TH1 cell function.