Ameliorating effects of the immunomodulator 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole in an experimental model of colitis in the rat.
The therapeutic efficacy of the immunomodulator 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (ST1959) in colonic inflammation was assessed in rats. One hour following colonic instillation of ethanolic 2,4,6-trinitrobenzene sulphonic acid (TNBS), intracolonic administration of 0.4 mg/kg ST1959 was started and continued once daily for 1 or 2 weeks. Daily administration of ST1959 for 1 week significantly reduced macroscopic and histological damage, myeloperoxidase activity, and colonic tissue levels of tumour necrosis factor-alpha and interferon-gamma. ST1959 did not affect interleukin-12 levels but significantly enhanced the production of interleukin-10 (sixfold increase). Two weeks of ST1959 treatment reduced the thickness of the colonic wall and myeloperoxidase activity to the same extent, and the histologic appearance of the mucosa was largely restored. The ameliorating effects seem to be ascribable to an impairment of both neutrophil infiltration/activation and tumour necrosis factor-alpha and interferon-gamma production, possibly consequent to the observed increase in the colonic tissue levels of the potent anti-inflammatory cytokine interleukin-10. Similar results were observed with the reference drug 5-aminosalycilic acid.
Stasi
Maria Antonietta
MA
Pharmacology Department-R&D, Sigma-tau S.p.A., Via Pontina km 30.400, 00040 Pomezia (RM), Italy. mariaantonietta.stasi@sigma-tau.it
Ruggiero
Vito
V
Ursillo
Angela
A
Taurelli
Roberto
R
Aglianò
Margherita
M
Weber
Elisabetta
E
Lorenzoni
Paola
P
Sorrentino
Vincenzo
V
Pacifici
Licia
L
Carminati
Paolo
P
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000201:enzymology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid
D016207:Cytokines; D007166:Immunosuppressive Agents; D014230:Triazoles; C030266:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase