Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia.
Phagocytes of the reticuloendothelial system are important in clearing systemic infection; however, the role of the reticuloendothelial system in the response to localized infection is not well-documented. The major goals of this study were to investigate the roles of phagocytes in the reticuloendothelial system in terms of bacterial clearance and inflammatory modulation in sepsis caused by Pseudomonas pneumonia. Macrophages in liver and spleen were depleted by administering liposome encapsulated dichloromethylene diphosphonate (clodronate) intravenously 36 h before the instillation of Pseudomonas aeruginosa into the lungs of anesthetized rabbits. Blood samples were analyzed for bacteria and cytokine concentrations. Lung injury was assessed by the bidirectional flux of albumin and by wet-to-dry weight ratios. Blood pressure and cardiac outputs decreased more rapidly and bacteremia occurred earlier in the clodronate-treated rabbits compared with the nondepleted rabbits. Plasma TNF-alpha (1.08 +/- 0.54 vs. 0.08 +/- 0.02 ng/ml) and IL-8 (6.8 +/- 1.5 vs. 0.0 +/- 0.0 ng/ml) were higher in the depleted rabbits. The concentration of IL-10 in liver of the macrophage-depleted rabbits was significantly lower than in normal rabbits at 5 h. Treatment of macrophage-depleted rabbits with intravenous IL-10 reduced plasma proinflammatory cytokine concentrations and reduced the decline in blood pressure and cardiac output. These results show that macrophages in the reticuloendothelial system have critical roles in controlling systemic bacteremia and reducing systemic inflammation, thereby limiting the systemic effects of a severe pulmonary bacterial infection.
Kurahashi
Kiyoyasu
K
Dept. of Anesthesiology and Critical Care Medicine, Yokohama City Univ. Graduate School of Medicine, Kanazawa-ku, Yokohama, 236-0004, Japan. kiyok@med.yokohama-cu.ac.jp
Sawa
Teiji
T
Ota
Maria
M
Kajikawa
Osamu
O
Hong
Keelung
K
Martin
Thomas R
TR
Wiener-Kronish
Jeanine P
JP
D000818:Animals; D016470:Bacteremia / Q000209:etiology / Q000401:mortality; D001794:Blood Pressure; D004002:Clodronic Acid / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D008081:Liposomes; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D055370:Lung Injury / Q000209:etiology / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D012157:Mononuclear Phagocyte System / Q000378:metabolism*; D010586:Phagocytes / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000209:etiology* / Q000401:mortality*; D011552:Pseudomonas Infections / Q000209:etiology* / Q000401:mortality*; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D011817:Rabbits; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D015996:Survival Rate
D016207:Cytokines; D008081:Liposomes; D004002:Clodronic Acid