Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia.

Full 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.

Author information

Author/s: Horino, Tetsuya (T); Matsumoto, Tetsuya (T); Ishikawa, Hiroki (H); Kimura, Soichiro (S); Uramatsu, Masashi (M); Tanabe, Masaaki (M); Tateda, Kazuhiro (K); Miyazaki, Shuichi (S); Aramaki, Yukihiko (Y); Iwakura, Yoichiro (Y); Yoshida, Masaki (M); Onodera, Shoichi (S); Yamaguchi, Keizo (K);

Affiliation: Department of Infectious Disease and Infection Control, The Jikei University School of Medicine, 3-19-18 Nishi-Shimbashi, Minato-ku, Tokyo, Japan.

Journal and publication information

Publication Type: Journal Article

Journal: Microbiology and immunology (Microbiol Immunol), published in Japan. (Language: eng)

Reference: 2009-Sep; vol 53 (issue 9) : pp 502-11

Dates: Created 2009/08/25; Completed 2009/10/13;

PMID: 19703244, status: MEDLINE (last retrieved date: 10/13/2009)

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