Review article: the pharmacological implications of leucocyte-endothelial cell interactions in Crohn's disease

Abstract

The importance of leucocyte-endothelial cell interactions in the inflammatory process is now recognized. In Crohn's disease, we have proposed that these interactions mediate not only the development of the parenchymal cell infiltrate, but also initiate a process (multifocal gastrointestinal infarction) that leads to ischaemic damage to the bowel wall. We review data on the actions of drugs in the treatment of Crohn's disease and, where known, we highlight their effects on leucocyte adhesion to the endothelium. Corticosteroids inhibit adhesion by inhibiting production of interleukin-1, tumour necrosis factor, interferon gamma, leukotrienes and platelet activating factor. Drugs liberating 5-aminosalicylate inhibit leukotriene production. Cyclosporin inhibits T-cell activation, and amplification of the immune response. Inhibition of leucocyte--endothelial cell interactions probably accounts for some of the beneficial effects of these drugs in Crohn's disease.