Controlled Trial of Azathioprine in Crohn's Disease

Willoughby, J. M. T.; J, Beckett; Kumar, Prashant; Dawson, A. M.

doi:10.1016/s0140-6736(71)90268-6

Cited by 293 publications

(122 citation statements)

References 12 publications

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“…Crohn's disease (CD), 3 but the mystery remains unsolved. The problem is that CD affects young adults, and there is no satisfactory therapy.…”

Section: E Fforts Have Been Made To Elucidate the Pathogenesis Ofmentioning

confidence: 99%

“…Corticosteroids are the most commonly used, but they only relieve the symptoms, without improvement of endoscopically visible lesions (2). Azathioprine and other immunosuppressive medications are also used, but their effectiveness in inducing remission remains controversial, and their utility is limited because of their side effects (3). Recently, anti-TNF-␣ mAb has been shown to be useful in patients with steroid-unresponsive CD (4).…”

Section: E Fforts Have Been Made To Elucidate the Pathogenesis Ofmentioning

confidence: 99%

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IL-6 Is Required for the Development of Th1 Cell-Mediated Murine Colitis

Yamamoto

Yoshizaki

Kishimoto

et al. 2000

The Journal of Immunology

394

259

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Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis of Crohn’s disease. Among those cytokines, strong expression of IL-6 has been repeatedly demonstrated. To examine the role for IL-6 in the pathogenesis of Crohn’s disease, we introduced anti-IL-6R mAb to a murine model of colitis. Colitis was induced in C.B-17-scid mice transferred with CD45RBhigh CD4+ T cells from BALB/c mice. Anti-IL-6R mAb or rat IgG was administered weekly after T cell transfer. ICAM-1 and VCAM-1 expression were analyzed by immunohistochemistry. Colonic cytokine expression was determined by RT-PCR. Mice treated with mAb showed normal growth, whereas controls lost weight. The average colitis score was 0.64 for mAb-treated mice and 1.80 for controls. T cell expansion in treated mice was less remarkable than in the controls. Colonic ICAM-1 and VCAM-1 expression were markedly suppressed by mAb. IFN-γ, TNF-α, and IL-1β mRNA were reduced by the treatment. The results presented here show a crucial role for IL-6 in the pathogenesis of murine colitis and suggest a therapeutic potential of anti-IL-6R mAb for treatment of human Crohn’s disease.

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“…Crohn's disease (CD), 3 but the mystery remains unsolved. The problem is that CD affects young adults, and there is no satisfactory therapy.…”

Section: E Fforts Have Been Made To Elucidate the Pathogenesis Ofmentioning

confidence: 99%

Section: E Fforts Have Been Made To Elucidate the Pathogenesis Ofmentioning

confidence: 99%

IL-6 Is Required for the Development of Th1 Cell-Mediated Murine Colitis

Yamamoto

Yoshizaki

Kishimoto

et al. 2000

The Journal of Immunology

394

259

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“…Some patients remain seriously ill with active disease after all therapeutic options have been exhausted [49][50][51]. Moreover, a distinct excessive mortality from CD exists in this group of patients [52][53][54][55].…”

Section: Crohn's Diseasementioning

confidence: 99%

Haematopoietic Cell Transplantation and Immunotherapy for Autoimmune Diseases in Children and Adults

Bitan¹

2011

Autoimmune Disorders - Current Concepts and Advances From Bedside to Mechanistic Insights

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“…More recently, studies have demonstrated that 6-thioguanine triphosphate (6-TGTP) inhibits Rac1 required for T-cell stimulation, resulting in T-cell apoptosis [Tiede et al 2003]. Kirsner and colleagues at the University of Chicago were amongst the first to show its efficacy in UC nearly 45 years ago [Bowen et al 1966], and it was subsequently shown to be beneficial in CD as well [Present et al 1980;Willoughby et al 1971].…”

mentioning

confidence: 99%