Gabriel Kenet, MD, Joram Wardi, MD, Yona Avni, MD, Hussein Aeed, PhD, Haim Shirin, MD, Liliana Zaidel, MD, Rami Hershkovitz, MD and Rafael Bruck, MD
Background: Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hypnotic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn’s disease, neutralization or suppression of TNFá reduces inflammation.
Objectives: To evaluate the effects of thalidomide in a model of experimental colitis.
Methods: Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined.
Results: Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNFá were significantly lower (P<0.05) in the treatment group (iodoacetamide + thalidomide) than the control group (iodoacetamide only). Histologically, colonic inflammation in the treated group was markedly decreased.
Conclusions: Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNFá, and should be further studied.
by Allan I. Bloom, MD, Talia Sasson, MD, Anthony Verstandig, MD, Yehuda G. Wolf, MD, Haim Anner, MD, Yakov Berlatzky, MD, Inna Akopnick, MD, Chaim Lotan, MD, Richard Lederman, MD and Pinchas D. Lebensart, MD
Larry W. Moreland, MD
There is accumulating evidence that tumor necrosis factor plays a major role in the pathogenesis of rheumatoid arthritis. Recent biotechnological advances have allowed for the development of agents that directly target TNF, a pro-inflammatory cytokine. In the last 2 years, the U.S. Food and Drug Administration and the European Union’s Commission of the European Communities have approved two biological agents for the treatment of refractory RA, etanercept and infliximab. Etanercept is a fusion protein, composed of the Fc portion of immunoglobulin G1 and the extracellular domain of a TNF receptor (p75). Infliximab is a chimeric monoclonal antibody composed of murine variable and human constant regions. In placebo-controlled trials, both agents have proven to be effective and well tolerated in PA patients.
Rafik Masalha, MD, Bella Chudakov, MD, Mohammed Morad MD, Inna Rudoy, MD, Ilia Volkov, MD and Itzhak Wirguin, MD