Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis: effects of probiotic treatment.
OBJECTIVE
The efficacy of probiotic organisms in the treatment of pouchitis has been reported. In the present study, we evaluated the tissue levels of pro- and anti-inflammatory cytokines, nitric oxide synthase, and matrix metalloproteinases in control and inflamed pouches before and after antibiotic and probiotic treatment of patients with acute pouchitis.


METHODS
Pouch biopsy samples were obtained from seven patients with pouchitis before and after antibiotic and probiotic treatment. Tissue samples from five patients with normal pouches were used as controls. Cytokines were determined by ELISA, matrix metalloproteinase activity was evaluated by zymograms, and nitric oxide synthase activity was determined by measuring arginine to citrulline conversion.


RESULTS
Tissue levels of tumor necrosis factor a increased (p < 0.01) in pouchitis relative to uninflamed pouches and reduced after antibiotic and probiotic treatment. Also, interferon y and interleukin 1alpha (IL-1alpha) augmented in pouchitis, but their increase did not reach statistical significance. The latter, however, were lower (p < 0.05) after treatment with the antibiotics and probiotics. Tissue levels of IL-4 and IL-10 were unchanged in inflamed pouches and unaffected by antibiotic treatment. However, IL-10 increased (p < 0.05) after probiotic treatment. Moreover, inflamed pouches had higher levels of inducible nitric oxide synthase and gelatinase activities, which decreased after treatment.


CONCLUSIONS
The ability of antibiotic and probiotic treatments to increase tissue levels of IL-10, at a higher level than those observed in control pouches, and to decrease, to levels present in control pouches, proinflammatory cytokine, inducible nitric oxide synthase, and matrix metalloproteinase activity may suggest a mechanism of action to explain the efficacy of this therapeutic regime in pouchitis.
Ulisse
S
S
Department of Experimental Medicine, University of L'Aquila, Italy.
Gionchetti
P
P
D'Alò
S
S
Russo
F P
FP
Pesce
I
I
Ricci
G
G
Rizzello
F
F
Helwig
U
U
Cifone
M G
MG
Campieri
M
M
De Simone
C
C
D000208:Acute Disease; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D019449:Pouchitis / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D019936:Probiotics / Q000627:therapeutic use*
D016207:Cytokines; D019001:Nitric Oxide Synthase; D020782:Matrix Metalloproteinases