title: Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia.
abstract: We evaluated the role of IL-1 during Pseudomonas aeruginosa bacteremia by intravenously injecting P. aeruginosa strain D4 into IL-1-deficient and WT mice. The two strains showed equivalent mortality rates. However, when the mice were pretreated with cyclophosphamide, bacteremia-induced mortality was significantly greater in the IL-1-deficient mice than in the WT mice (P < 0.01). We then investigated the role of neutrophils and macrophages in protecting IL-1-deficient mice from bacteremia by administering anti-Gr-1 antibody or liposomes containing dichloromethylene diphosphonate, respectively. After P. aeruginosa inoculation survival was significantly lower in the macrophage-depleted IL-1-deficient mice than in the WT mice. In contrast, neutrophil depletion did not have this effect. Compared to the macrophage-depleted WT mice, the macrophage-depleted IL-1-deficient bacteremic mice had higher bacterial counts in various organs 48 and 72 hr post-infection. They also had lower TNF-alpha, IL-6, and INF-gamma concentrations in their livers during the early phase of sepsis. Thus, IL-1 deficiency becomes disadvantageous during P. aeruginosa bacteremia when it is accompanied by immunosuppression, particularly when macrophage functions are seriously impaired.
authors.affiliation: Department of Infectious Disease and Infection Control, The Jikei University School of Medicine, 3-19-18 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: Hiroki
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
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: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Shoichi
authors.initials: S
authors.lastname: Onodera
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D007165:Immunosuppression Therapy; D007375:Interleukin-1 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000502:physiology*
chemical_list: D007375:Interleukin-1