Immunopharmacology of 5-aminosalicylic acid and of glucocorticoids in the therapy of inflammatory bowel disease

Glucocorticoids as well as 5-aminosalicylic acid have been used-successfull y in different formulations during the past 40 years for the treatment of b oth acute and:chronic inflammation in inflammatory bowel disease. The mecha nism by which the drugs exert their: actions are only partially known. Rece nt studies of the immunoregulation in the lamina propria provide evidence t hat; numerous therapeutic mechanisms contribute to the efficacy of these dr ugs including the inhibition of arachidonic acid metabolism, a decrease in radical formation by oxygen radical scavenging, an inhibition of both in vi vo and in vitro activation of peripheral and intestinal lymphocytes. Moreov er direct immunoregulatory effects exerted by the drug may be important in influencing the complex balance of pro-inflammatory mechanisms during activ e intestinal inflammation. Such effects are the inhibition of both peripher al and intestinal B lymphocyte immunoglobulin secretion as well as the inhi bition of pro-inflammatory cytokine production and their binding to recepto rs. Some of these immunoregulatory effects appear to be mediated:by an inhi bition of the activation of the nuclear factor kappa B transcription factor family by steroids and (less potent) aminosalicylic acid. Activation of nu clear factor kappa B appears to be pivotal for the sustained upregulation o f inflammation molecule expression in many inflammatory diseases. It seems, therefore, most likely that the enormous therapeutic potency of steroids, as well as the anti-inflammatory properties of 5-aminosalacylic acid, are n ot achieved by a single action of the drug. The complex orchestration of nu merous inhibitory interactions with pro-inflammatory principles will add to the therapeutic potential of steroids and of 5-aminosalacylic acid in the treatment of both acute and chronic intestinal inflammation.