[A clinical trial of rosiglitazone and 5-aminosalicylate combination for ulcerative colitis].
OBJECTIVE
To investigate the therapeutic effects of the combination of rosiglitazone, which is peroxisome proliferators-activated receptor gamma (PPARgamma) ligands used to treat type 2 diabetes mellitus, and aminosalicylate on mildly or moderately active ulcerative colitis and on relevant cytokine expressions.


METHODS
According to the national guideline of China for diagnosis and treatment of the inflammatory bowel disease (IBD), 42 patients with mild, moderately active ulcerative colitis were selected from the outpatient clinic of West China Hospital from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure were excluded, as well as those who had received corticosteroid or immunosuppressant treatment within the last month. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group with rosiglitazone 4 mg/d plus 5-aminosalicylic acid (5-ASA) 2 g/d or sulfasalazine 3 g/d and the control group with 5-ASA or sulfasalazine alone for 4 weeks. Clinical and histological changes were evaluated weekly by the Mayo scoring system for assessment of the activity of ulcerative colitis and the Truelove-Richards' grading system, respectively. PPARgamma and nuclear factor (NF)-kappaB p65 expressions in colonic mucosa were investigated before and after the treatment.


RESULTS
Mayo scores decreased 4.01 in treatment group and 3.48 in control group respectively, with a remission rate 71.4% in treatment group and 57.1% in control group respectively. Along with the improvement of the Mayo score, the histological grade improvement was more significant in treatment group than in control group (P < 0.05). PPARgamma expression was higher, and NF-kappaB p65 positive rate was lower in treatment group than in control group after the treatment, and there was a good negative correlation between PPARgamma and NF-kappaB.


CONCLUSIONS
Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. The PPARgamma expression was lower in active ulcerative colitis. Rosiglitazone alleviate colonic inflammation probably the through blockade of NF-kappaB, which can be a novel approach to the ulcerative colitis treatment.
Liang
Hong-liang
HL
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.
Ouyang
Qin
Q
D000293:Adolescent; D000328:Adult; D000636:Aminosalicylic Acids / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis; D047495:PPAR gamma / Q000096:biosynthesis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D000636:Aminosalicylic Acids; D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone