Inflammatory mediator changes in cotton-top tamarins (CTT) after SC-41930 anti-colitic therapy

Abstract

Use of the CTT model provides insight into the inflammatory mediator contribution in the pathogenesis of idiopathic colitis. To evaluate anti-colitic efficacy, the leukotriene B₄ receptor antagonist and anti-inflammatory agent, SC-41930, was administered (10 mg/kg BW by gavage BID) for 8 weeks to CTTs with histologically confirmed persistent and defined active colitis. The inflammatory mediators LTB₄, PGE₂, TXB₂, and PAF were assayed in colonic dialysate that was collected after 11/2 h from four CTTs pre-, mid-, and post-treatment, frozen at −70°C, and analyzed by RIA after HPLC purification. LTB₄ levels were lower at mid- and post-treatment and had little inter-animal variation post-treatment. PGE₂ and PAF levels were elevated during SC-41930 treatment, but there was a trend towards lower thromboxane B₂ levels. Reduced LTB₄ (PMN degranulation and chemotaxis) and increased PGE₂ (mucosal-protective effect) may, in part, explain the observed efficacy of SC-41930 in active tamarin colitis.