IL-1 IS AN IMPORTANT MEDIATOR FOR MICROCIRCULATORY CHANGES IN ENDOTOXIN-INDUCED INTESTINAL MUCOSAL DAMAGE

Although small intestine is frequently injured in endotoxin shock, the exact pathological sequence has not been fully understood. The major objective of this study is to elucidate the role of interleukin (IL)-1 in endotoxin-induced microcirculatory disturbance of rat small intest ine. Mucosal and submucosal microvessels of the rat ileum were observe d by intravital microscope with a high speed video camera system and t he attenuating effect of E5090, an inhibitor of IL-1 generation, on en dotoxin-induced intestinal microcirculatory disturbances was investiga ted. Endotoxin infusion produced significant mucosal damage, but befor e these morphological changes became significant, microvascular stasis in villi, decreased red blood cell velocity, and increased leukocyte adherence to venular walls were observed in intestinal microcirculator y beds 30 min after endotoxin administration. Intestinal IL-1 alpha le vels were also significantly increased at that time. Endotoxin treatme nt enhanced chemiluminescence activity from neurophils and rapidly mob ilized CD18 on leukocytes. E5090, which suppressed the IL-1 production in intestinal mucosa, attenuated the microcirculatory disturbances in duced by endotoxin, and significantly reduced the subsequent mucosal d amage. E5090 also attenuated the increased chemiluminescence activity and CD18 expression on leukocytes. In conclusion, the production of IL -1 alpha is enhanced in the intestinal mucosa during endotoxin infusio n. IL-1 may be an important mediator of microcirculatory changes, incl uding decreased red blood cell velocity and increased leukocyte sticki ng and its activation, leading to the mucosal damage.