Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia |
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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 |
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Institution: | Department of Infectious Disease and Infection Control, The Jikei University School of Medicine, 3-19-18 Nishi-Shimbashi, Minato-ku;, Department of Microbiology, Tokyo Medical University;, Department of Microbiology and Infectious Diseases, Toho University Faculty of Medicine;, School of Pharmacy, Tokyo University of Pharmacy and Life Science;and Division of Cell Biology, Center of Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan |
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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-α, IL-6, and INF-γ 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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Keywords: | interleukin-1 macrophage depletion neutropenia Pseudomonas aeruginosa |
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