Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia.
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| 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.
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| Authors | Tetsuya Horino, Tetsuya Matsumoto, Hiroki Ishikawa, Soichiro Kimura, Masashi Uramatsu, Masaaki Tanabe, Kazuhiro Tateda, Shuichi Miyazaki, Yukihiko Aramaki, Yoichiro Iwakura, Masaki Yoshida, Shoichi Onodera, Keizo Yamaguchi |
| Journal | Microbiology and immunology (Microbiol Immunol) Vol. 53 Issue 9 Pg. 502-11 (Sep 2009) ISSN: 0385-5600 [Print] Australia |
| PMID | 19703244 (Publication Type: Journal Article) |
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