Interleukin-1 deficiency in combination with macrophage depletion increases susceptibility to Pseudomonas aeruginosa bacteremia.
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.
Horino
Tetsuya
T
Department of Infectious Disease and Infection Control, The Jikei University School of Medicine, 3-19-18 Nishi-Shimbashi, Minato-ku, Tokyo, Japan.
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
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*
D007375:Interleukin-1