PROSTAGLANDINS IN INFLAMMATORY BOWEL-DISEASE THERAPY

Because the etiology of inflammatory bowel disease (IBD) is unknown, a ttempts to find new therapies for this disease have focused on the sol uble mediators that maintain and amplify the inflammatory response. Th e two major classes of mediators derived from membrane phospholipids a re the metabolites arachidonic acid (eicosanoids) and platelet activat ing factor. These metabolites are major mediators in the processes of inflammation and the stimulation of intestinal secretion of water and electrolytes found in IBD. It is clear that the interaction between pr ostaglandins and leukotrienes is complex being both additive and antag onistic and, in this regard, it is impossible to separate the summatio n of their effects. Nevertheless, over the past several years, it has become clear that inhibition of leukotrienes using leukotriene biosynt hesis inhibitors, leukotriene receptor antagonists or eicosapentanoic acid is beneficial in preventing and/or healing both experimentally-in duced and human forms of IBD. In contrast, inhibition of prostaglandin s does not improve experimentally-induced colitis and, in humans, may actually exacerbate the disease. By implication, leukotrienes may be i njurious while prostaglandins are protective to intestinal mucosa. The mucosal protective effect of the prostaglandin analogue, misoprostol, during experimentally-induced colitis is not the consequence of alter ations in bloodflow but rather the consequence of accelerated rate of restitution and repair. It remains to be determined whether the benefi cial effects of prostaglandins in experimentally-induced models of col itis would also occur in human IBD.