ストレス潰瘍の発生メカニズムにおけるサイトカインの役割 : 「免疫-脳-胃腸」軸の存在(心身症の発症メカニズム-各科領域から)

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We have recently reported that interleukin-1 (IL-1), a cytokine produced mainly by activated monocytes and macrophages, protects the gastric mucosa against ulcerogenic stress and that this anti-ulcer action of IL-1 is mediated by the central nervous system. On the basis of these findings, we have proposed the possible existence of an "immune-brain-gut" axis, which may play an important role in the immunoneuroendocrine regulation of gastric mucosal protection. In the present study, we addressed a mechanism whereby IL-1 exhibits its protective action for the gastric mucosa, using male Wistar rats weighing approximately 200 g. Recombinant human ILl β at various doses (1,10 and 100 ng/rat) was i, c, v. administered. Central IL-1 inhibited gastric acid secretion in a dose-related manner in pylorus-ligated rats. This antisecretory action of IL-1 was completely diminished by pretreatment with indomethacin (2 mg/kg, i. p.), a blocker of prostaglandin (PG) biosynthesis. Similarly, the central injection of IL-1 dose-dependently suppressed gastric emptying in conscious rats. Interesting enough, however, the preinjection of indomethacin failed to alter the inhibitory action of IL-1 on gastric emptying, suggesting that the suppressive effects of IL-1 on gastric functions are mediated by different mechanisms, i.e., PG-dependent or PG-independent. Next, we examined the effects of IL-1 in experimental ulcer models : water-immersion restraint stress and intragastric administration of absolute ethanol. Central IL-1 protected the gastric mucosa against both ulcerogenic stimuli. These results suggest that the mucosal protective effects of IL-1 depend largely on its inhibitory actions on gastric secretion and motility, two important aggressive factors in terms of the pathogenesis of ulcer formation, but it is also possible that other mechanisms including the PG system in the stomach may contribute to the anti-ulcer actions of IL-1. All these data imply that gastric ulcer is not simply a local disease in the stomach, but a general disease involving even the immune system, not to mention the brain. We firmly believe that these novel approaches from an immunoneuroendocrine point of view will bring out a breakthrough for a better understanding of the pathogenesis and pathophysiology of stress ulcer, which in turn will lead to the development of new therapeutic strategies.
日本心身医学会の論文
1994-03-01

ストレス潰瘍の発生メカニズムにおけるサイトカインの役割 : 「免疫-脳-胃腸」軸の存在(心身症の発症メカニズム-各科領域から)

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