Sulphasalazine metabolites in experimental inflammation: Modulation of neutrophil function

Abstract

Sulphasalazine is widely used in the treatment of inflammatory bowel disease. Its exact mode of action is unclear, but experimental evidence suggests that the active moiety, 5-aminosalicylic acid (5-ASA), modulates all or most of the functions of neutrophils during acute inflammation. These comprise adhesion to vascular endothelium, migration through the vessel wall in response to a chemotactic gradient, and the release of cytotoxic oxidants and proteases. In vitro, 5-ASA has been shown to reduce both neutrophil adhesion and leukotriene B4-mediated chemotaxis. It also provides significant protection against neutrophil-mediated increases in mucosal permeability induced by naturally occurring inflammatory mediators such asN-formyl-methionine-leucine-phenylalanine (fMLP). Which specific neutrophil function is modulated by 5-ASA to provide the latter effect remains unclear, but there is considerable evidence to indicate that it may both scavenge neutrophil-derived oxidants and inhibit their generation. Although such experimental evidence suggests that 5-ASA acts by modulation of neutrophil functions in patients with IBD, this remains speculation. Additional work is needed to define more clearly the therapeutic significance of the neutrophilic actions of 5-ASA.