Therapeutic effect of the immunomodulator glatiramer acetate on trinitrobenzene sulfonic acid induced experimental colitis
Küçük Resim Yok
Dosyalar
Tarih
2005
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Inflammatory Bowel Diseases
Erişim Hakkı
info:eu-repo/semantics/embargoedAccess
Özet
Inflammatory bowel diseases are characterized by detrimental immune reactivity in the gut and imbalance between proinflammatory and antiinflammatory reactivity. In an attempt to downregulate inflammatory bowel disease, we tested whether the immunomodulator glatiramer acetate (GA; Copaxone®, copolymer 1), an approved drug for the treatment of multiple sclerosis, can ameliorate trinitrobenzene sulfonic acid (TNBS)-induced colitis, a murine model that resembles human Crohn's disease. Experimental colitis was induced by rectal instillation of TNBS in 3 mice strains: BALB/c, SJL/J, and (SJL/JXBALB/c)F1, and its severity was evaluated by gross colon injury, histologic damage, body weight, and survival rate. We studied the effect of GA on all these parameters as well as on lymphocyte reactivity manifested by proliferation and secretion of tumor necrosis factor-α, and transforming growth factor-β. GA treatment significantly suppressed the various manifestations of TNBS-induced colitis as demonstrated by substantial reduction in the macroscopic colonic damage, preservation of the microscopic colonic structure, reduced weight loss, and improved long-term survival, in GA treated mice compared with untreated mice. The parenteral route was more effective than the oral route. GA suppressed the proliferation of local mesenteric lymphocytes to syngeneic colon extract and the detrimental tumor necrosis factor-α secretion. In addition, it induced a beneficial secretion of transforming growth factor-β. The ability of GA to effectively modulate the clinical manifestations and the detrimental immune response involved in experimental colitis warrants further studies to determine the clinical efficacy of GA in the treatment of human inflammatory bowel diseases.
Açıklama
Anahtar Kelimeler
Kaynak
Inflammatory Bowel Diseases
WoS Q Değeri
Scopus Q Değeri
Cilt
11
Sayı
2
Künye
Aharoni, R. Kayhan, B. Arnon, R. (2005). Therapeutic effect of the immunomodulator glatiramer acetate on trinitrobenzene sulfonic acid induced experimental colitis. Inflammatory Bowel Diseases, 11(2), 106–115.
