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This Article Full Text Full Text (PDF) All Versions of this Article: 296/2/L198    most recent 90472.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kurahashi, K. Articles by Wiener-Kronish, J. P. Search for Related Content PubMed PubMed Citation Articles by Kurahashi, K. Articles by Wiener-Kronish, J. P.

Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia

¹Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan; ²Department of Anesthesia, The University of California at San Francisco, San Francisco, California; ³Medical Research Service, Veterans Affairs Puget Sound Health Care System and the Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington; ⁴Department of Biopharmaceutical Sciences, The University of California at San Francisco, San Francisco, California; and ⁵Department of Anesthesia and Perioperative Care, Department of Medicine, and Cardiovascular Research Institute, The University of California at San Francisco, San Francisco, California

Submitted 5 September 2008 ; accepted in final form 14 November 2008

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- (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.

counterregulatory response; bacterial clearance; macrophages