title: IL-1 is an important mediator for microcirculatory changes in endotoxin-induced intestinal mucosal damage.
abstract: 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 intestine. Mucosal and submucosal microvessels of the rat ileum were observed by intravital microscope with a high speed video camera system and the attenuating effect of E5090, an inhibitor of IL-1 generation, on endotoxin-induced intestinal microcirculatory disturbances was investigated. Endotoxin infusion produced significant mucosal damage, but before 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 microcirculatory beds 30 min after endotoxin administration. Intestinal IL-1alpha levels were also significantly increased at that time. Endotoxin treatment enhanced chemiluminescence activity from neurophils and rapidly mobilized CD18 on leukocytes. E5090, which suppressed the IL-1 production in intestinal mucosa, attenuated the microcirculatory disturbances induced by endotoxin, and significantly reduced the subsequent mucosal damage. E5090 also attenuated the increased chemiluminescence activity and CD18 expression on leukocytes. In conclusion, the production of IL-1alpha is enhanced in the intestinal mucosa during endotoxin infusion. IL-1 may be an important mediator of microcirculatory changes, including decreased red blood cell velocity and increased leukocyte sticking and its activation, leading to the mucosal damage.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Fukumura
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: I
authors.initials: I
authors.lastname: Kurose
authors.forename: H
authors.initials: H
authors.lastname: Higuchi
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Ebinuma
authors.forename: J Y
authors.initials: JY
authors.lastname: Han
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: G
authors.initials: G
authors.lastname: Wakabayashi
authors.forename: M
authors.initials: M
authors.lastname: Kitajima
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D018821:CD18 Antigens / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D004731:Endotoxins; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D004926:Escherichia coli; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000032:analysis / Q000502:physiology*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000737:chemistry; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology*; D009284:Naphthols / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000179:Acrylates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018821:CD18 Antigens; D004731:Endotoxins; D007375:Interleukin-1; D009284:Naphthols; D014409:Tumor Necrosis Factor-alpha; C069676:E 5090