Ulisse et al. (51) evaluated in a non blinded study the tissue levels of pro- and anti-inflammatory cytokines, NOS, and matrix metalloproteinases (MMP) both in control and inflamed pouches before and after antibiotic and probiotic treatment of patients with acute pouchitis.
The results of this study demonstrated that VSL#3 is able to induce a significant increase in the expression of the antiinflammatory cytokine IL-10 in the mucosal pouch compared to inflamed and antibiotic-treated patients. Antibiotic treatment reduced the expression of the proinflammatory cytokines IFN-y and TNF-cx but not IL-1cx. All three cytokines decreased further, in a statistically significant manner, after VSL#3 treatment.
Inflamed pouch tissue increased the levels of the inducible NOS (iNOS) and MMP activity. iNOS and MMP activity were reduced after antibiotic and probiotic treatment. The ability to increase IL-10 to a higher level than that observed in control pouches and to decrease proinflammatory cytokines and iNOS and MMP activity tissue levels to levels present in control pouches may suggest a mechanism of action that would explain the benefits of probiotics as maintenance treatment of patients with pouchitis.
iNOS plays an important role in modulating macrophage cellular function during inflammation and its level increases after stimulation with cytokines such as IL-1, TNF-cx and IFN-y. NOS activity levels were monitored in control and inflamed pouch tissues, and following antibiotic and probiotic activity an increase of iNOS activity was observed. Antibiotic treatment induced partial but significant reduction in iNOS activity level (1.0 ± 0.5 pmol/mg protein/min). This decrease was more pronounced, and statistically significant, after treatment with VSL3.
MMP expression and activation play important roles in inflammatory processes and in the pathogenesis of inflammatory diseases. Macrophages and T-cells produce several MMPs and their expression is modulated by cytokines. MMPs degrade the basal membrane and extracellular matrix and are important to leukocyte migration and to the release of TNF-cx from its membrane-bound form. TNF-cx is a potent pro-inflammatory agent produced primarily by activated monocytes and macrophages.
These studies demonstrated that probiotics may increase the pouch tissue level of IL-10 to a higher level than the observed in control pouches. On the other hand, they may reduce tissue levels of the pro-inflammatory cytokines IL-1cx, IFN-y and TNF-cx to levels present in control pouches. This effect may be in turn responsible for the down-regulation of iNOS and MMP activity.