FR167653, a potent suppressant of interleukin‐1 and tumor necrosis factor‐α production, ameliorates colonic lesions in experimentally induced acute colitis¹

Abstract

Subcutaneous administration of FR167653 was able to ameliorate the acute changes induced by acetic acid instillation in a dose-dependent manner. This is the first report to evaluate the dual inhibition of the production of IL-1 and TNF-alpha, offered by FR167653, in acute experimental colitis. Further studies are necessary to evaluate FR167653's efficacy and safety on long-term conditions.

Melatonin reduces bacterial translocation and apoptosis in trinitrobenzene sulphonic acid-induced colitis of rats

“…This finding is in agreement with earlier investigators who suggested a critical role of neutrophils in colitis [28] . Infiltration and activation of neutrophils lead to excessive generation of proinflammatory cytokines and reactive oxygen species that have been implicated in the pathogenesis of colitis [29] . The decrease in the expression of TNF-α in the melatonin-treated rats supported these findings.…”

FR167653 reduces obliterative airway disease in rats

“…FR originally was found to inhibit TNF-␣ and IL-1␤ production in human peripheral lymphocytes and monocytes via a specific p38-dependent pathway. 12 That work began attempts to characterize the specific role of p38 in various disease processes, such as colitis, 13 ischemia-reperfusion injury of liver, 14 kidney 15 and heart, 16 and arthritis 17 and gastritis. 18 With specific reference to lung injury models, FR has been protective in models of direct ischemia-reperfusion injury 19 and lipopolysaccharide-induced lung injury.…”

Reduced Severity of a Mouse Colitis Model with Angiotensin Converting Enzyme Inhibition

“…TNF-α is well established as a major trigger of apoptosis in numerous cell lines (8), and in addition, the high rate of apoptosis and mucosal injury in UC appears to be mediated by an increase in TNF-α (9,10). Therapies that reduce epithelial cell apoptosis and TNF-α levels have led to clinical and histologic improvements in experimental models of colitis (2,11).…”