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 successfully in different formulations during the past 40 years for the treatment of both acute and chronic inflammation in inflammatory bowel disease. The mechanism by which the drugs exert their actions are only partially known. Recent studies of the immunoregulation in the lamina propria provide evidence that numerous therapeutic mechanisms contribute to the efficacy of these drugs including the inhibition of arachidonic acid metabolism, a decrease in radical formation by oxygen radical scavenging, an inhibition of both in vivo and in vitro activation of peripheral and intestinal lymphocytes. Moreover direct immunoregulatory effects exerted by the drug may be important in influencing the complex balance of pro-inflammatory mechanisms during active intestinal inflammation. Such effects are the inhibition of both peripheral and intestinal B lymphocyte immunoglobulin secretion as well as the inhibition of pro-inflammatory cytokine production and their binding to receptors. Some of these immunoregulatory effects appear to be mediated by an inhibition of the activation of the nuclear factor kappa B transcription factor family by steroids and (less potent) aminosalicylic acid. Activation of nuclear factor kappa B appears to be pivotal for the sustained upregulation of 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-aminosalicylic acid, are not achieved by a single action of the drug. The complex orchestration of numerous inhibitory interactions with pro-inflammatory principles will add to the therapeutic potential of steroids and of 5-aminosalicylic acid in the treatment of both acute and chronic intestinal inflammation.