PLATELET-ACTIVATING-FACTOR MEDIATES TRINITROBENZENE INDUCED COLITIS

Platelet-activating factor (PAF) is an endogenous phospholipid which m ay be an important mediator of shock and inflammation. Recent evidence suggests that PAF plays a role in the development of ischemic colitis and inflammatory bowel disease. Its effects are mediated by second me ssengers, including the arachidonic acid metabolites. Using an ex vivo isolated left colon rabbit perfusion model, our aims were to determin e whether exogenously administered trinitrobenzene sulfonic acid (TNB) , which produces experimental colitis, stimulates both PAF and eicosan oid release in the colon, and if so, whether this effect can be blocke d by a PAF antagonist. Colonic inflammation was induced by the intraco lonic administration of 0.25 ml of 50% ethanol containing 30 mg of TNB . Tissue and perfusate concentrations of the eicosanoids, [prostagland in E (PGE(2)), 6-keto-prostaglandin F-1 alpha, 6-keto-PGF(1 alpha) and thromboxane B-2 (TXB(2)), leukotriene B-4 (LTB(4))] and the autocoid PAP were measured by ELISA. During TNB infusion there was a significan t increase in tissue levels of PAP compared to control colons. Additio nal studies performed pretreating the colons with the PAF receptor ant agonist WEB-2170 prior to TNB infusion blocked PAF release. TNB stimul ated release of luminal eicosanoids except LTB(4) and suppressed relea se of tissue prostanoids, Pretreatment with WEB-2170 prior to TNB inhi bited luminal eicosanoids, and inhibited PGE(2) and prostacyclin, but not TX tissue suppression. Inhibition of TNB-stimulated PAF release by WEB-2170 suggests that PAF may play a role in TNB-induced colitis and this phenomenon may mediate tissue injury.