Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat

The histamine H-4 receptor is a G-protein coupled receptor with little homology to the pro-inflammatory histamine H, receptor, expressed on cells of the immune system with hematopoietic lineage such as eosinophils and mast cells. The effects of the recently described highly selective histamine H-4 receptor antagonists JNJ 10191584 and JNJ 7777120 have now been investigated on the acute colitis provoked by trinitrobenzene sulphonic acid over 3 days in the rat. Treatment with JNJ 10191584 (10-100 mg/kg p.o., b.i.d.) caused a dose-dependent reduction in macroscopic damage, inhibition of the TNBS-provoked elevation of both colonic myeloperoxidase and tumour necrosis factor-alpha (TNF-alpha), and a reduction in the histologically assessed increase in mucosal and submucosal thickness and neutrophil infiltration. JNJ 7777120 (100 mg/kg p.o., b.i.d.) likewise reduced the macroscopic injury and the increases in colonic myeloperoxidase and TNF-alpha levels. These findings indicate a pro-inflammatory role for the histamine H-4 receptor in this model and suggest a novel pharmacological approach to the treatment of colitis. (c) 2005 Elsevier B.V All rights reserved.