Methotrexate is effective in reactivated colitis and reduces inflammatory alterations in mesenteric adipose tissue during intestinal inflammation.
Mesenteric white adipose tissue hypertrophy and modifications in adipocytokine production are described features of Crohn's disease. Experimentally, mesenteric white adipose tissue alterations, associated with intestinal inflammation, can be induced in a model of reactivated colitis by repeated administration of intrarectal trinitrobenzenosulfonic acid (TNBS) in ethanol solution. Crohn's disease patients refractory to corticosteroid treatment are frequently treated with methotrexate; however, there is no information regarding the drug's effect on adipose tissue alterations and in a reactivated colitis experimental model. Thus, we evaluated the effect of methotrexate upon mesenteric WAT alterations and inflammatory features in experimental colitis in rats. Colitis status was evaluated by macroscopic score, histopathological analysis, myeloperoxidase activity, TNF-alpha and IL-10 expression, as well as iNOS and TLR-4 expression in colon samples. The adipose tissue alterations were assessed by TNF-alpha, IL-10, leptin and adiponectin production, as well as by macrophage infiltration evaluation. Methotrexate exerts an anti-inflammatory activity in experimental reactivated colitis by regulating the shift from Th1 to Th2 cytokines, reducing TNF-alpha and improving IL-10 production. Additionally, methotrexate reduces other inflammatory parameters in the colon, such as iNOS and TLR-4 expression. In mesenteric white adipose tissue, methotrexate treatment reduces the production of pro- and anti-inflammatory adipocytokines as well as macrophage infiltration, suggesting that immunosuppressant drugs diminish adipose tissue inflammatory alterations associated with intestinal inflammation.
Thomaz
Marcia Aparecida
MA
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, 12916-900 Bragança Paulista, SP, Brazil.
Acedo
Simone Coghetto
SC
de Oliveira
Caroline Candida
CC
Pereira
José Aires
JA
Priolli
Denise Gonçalves
DG
Saad
Mario José
MJ
Pedrazzoli
José
J
Gambero
Alessandra
A
D000273:Adipose Tissue / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D000818:Animals; D002465:Cell Movement; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016207:Cytokines / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D007166:Immunosuppressive Agents; D008727:Methotrexate