title: 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.
abstract: 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.
authors.affiliation: Pharmacology Department-R&D, Sigma-tau S.p.A., Via Pontina km 30.400, 00040 Pomezia (RM), Italy. mariaantonietta.stasi@sigma-tau.it
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Stasi
authors.forename: Vito
authors.initials: V
authors.lastname: Ruggiero
authors.forename: Angela
authors.initials: A
authors.lastname: Ursillo
authors.forename: Roberto
authors.initials: R
authors.lastname: Taurelli
authors.forename: Margherita
authors.initials: M
authors.lastname: Aglianò
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Weber
authors.forename: Paola
authors.initials: P
authors.lastname: Lorenzoni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sorrentino
authors.forename: Licia
authors.initials: L
authors.lastname: Pacifici
authors.forename: Paolo
authors.initials: P
authors.lastname: Carminati
mesh_terms: 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
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D014230:Triazoles; C030266:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase