Increased expression of cytokines, inducible nitric oxide synthase and matrix metalloproteinases in pouchitis: Effects of probiotic treatment.

Pouchitis is the most common complication following ileal pouch-anal anastomosis for ulcerative colitis. The efficacy of probiotic organisms in the treatment of chronic pouchitis has been recently reported (Gastroenterology 119: 305, 2000). In the present study, we evaluated the tissue level of pro- and anti-inflammatory cytokines, nitric oxide synthase (NOS) and matrix metalloproteinases (MMP) in control and inflamed pouch before and after antibiotic and probiotic treatment of patients with pouchitis. METHODS: Seven patients with active pouchitis received an antibiotic treatment (rifaximin 2 g/day and ciprofloxacin 1 g/day) for one month and after remission were treated for 9 months with 6 grams per day of a highly concentrated probiotic preparation, VSL#3, containing 4 strains of lactobacilli, 3 strains of bifidobacteria and one streptococcus strain (VSL Pharmaceuticals). Tissue samples of 5 patients with normal pouch have been used as control. Cytokine tissue levels were determined by ELISA. MMP activity was evaluated by zymograms and NOS activity by measuring arginine to citrulline conversion. RESULTS: Tissue levels of IFN-gamma and TNF-alpha were significantly increased (Pa<0.05) in pouchitis compared to uninflamed pouches and significantly reduced after antibiotic and probiotic treatment (Pa<0.05). IL-l0, but not IL-4, was increased following probiotic treatment (Pa<0.05). Moreover, inflamed pouches showed augmented levels of inducible NOS, MMP-2 and MMP-9 activities which were reduced following treatments. CONCLUSION: The ability to increase IL-l0 and to decrease pro-inflammatory cytokines, inducible NOS and MMPs activity tissue levels by antibiotic and probiotic treatment may explain the efficacy of this therapeutic regime in active pouchitis.