title: Interleukin-1-deficient mice exhibit high sensitivity to gut-derived sepsis caused by Pseudomonas aeruginosa.
abstract: BACKGROUND
  The role of interleukin (IL)-1 in infectious diseases is controversial; some investigators indicated an enhancing effect of IL-1 on host resistance whereas others demonstrated the protective role of IL-1 receptor antagonist in infection. We evaluated the role of endogenous IL-1 in gut-derived sepsis caused by Pseudomonas aeruginosa, by comparing IL-1-deficient mice and wild-type (WT) mice.
  
  
  METHODS
  Gut-derived sepsis was induced by intraperitoneal injection of cyclophosphamide after colonization of P. aeruginosa strain D4 in the intestine.
  
  
  RESULTS
  The survival rate of IL-1-deficient mice was significantly lower than that of WT mice (P<0.01). Bacterial counts in the liver, mesenteric lymph node and blood were significantly higher in IL-1-deficient mice than in WT mice. Tumor necrosis factor alpha and IL-6 in the liver were significantly higher in IL-1-deficient mice than in WT mice. In vitro, phagocytosis and cytokine production by macrophages were impaired in IL-1-deficient mice compared with WT mice.
  
  
  CONCLUSIONS
  Our results indicate a critical role for IL-1 during gut-derived P. aeruginosa sepsis. The results also suggest that both impairment of cytokine production and phagocytosis by macrophages are caused by IL-1 deficiency and lead to impaired host response.
authors.affiliation: Department of Internal Medicine, Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Horino
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Uramatsu
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Akio
authors.initials: A
authors.lastname: Nakane
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism; D002470:Cell Survival; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D020022:Genetic Predisposition to Disease; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D007962:Leukocytes / Q000166:cytology; D008099:Liver / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D018805:Sepsis / Q000235:genetics* / Q000382:microbiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003520:Cyclophosphamide