Sulphasalazine metabolites in experimental inflammation: Modulation of neutrophil function

Autor: Matthew B. Grisham, D. N. Granger, C. Von Ritter
Rok vydání: 1993
Předmět:
Zdroj: InflammoPharmacology. 2:201-207
ISSN: 1568-5608
0925-4692
DOI: 10.1007/bf02660612
Popis: 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.
Databáze: OpenAIRE