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EFFECTS OF Cl2MDP-ENCAPSULATING LIPOSOMES IN A MURINE MODEL OFPSEUDOMONAS AERUGINOSA-INDUCED SEPSIS
- Source :
- Journal of Liposome Research. 12:239-257
- Publication Year :
- 2002
- Publisher :
- Informa UK Limited, 2002.
-
Abstract
- Pseudomonas aeruginosa is a pathogen that frequently causes acute lung injury, bacteremia and sepsis in critically ill patients. As tissue macrophages are a major producer of inflammatory mediators that contribute to septic physiology, and are essential for eliminating bacteria from the circulation, we investigated the role of tissue macrophages in the generation of both inflammatory and anti-inflammatory cytokines in septic shock by using our mouse model of P. aeruginosa pneumonia. To see the effects of tissue macrophage depletion, we intravenously injected dichloromethylene-diphosphonate (Cl2MDP)-encapsulating liposomes in mice. Two days after the liposome injection, we instilled cytotoxic P. aeruginosa (PA103) into the lung that disseminates and causes septic shock. After the infection, we collected blood and bronchoalveolar lavage fluids. The samples were then analyzed for TNF-alpha, MIP-2, and IL-10 concentration. We compared these results to control mice that received either liposomes without Cl2MDP or phosphate buffered saline alone. Plasma TNF-alpha, MIP-2, and IL-10 levels were significantly decreased in the tissue macrophage-depleted mice compared to the control groups of mice. Although depletion of tissue macrophages by Cl2MDP-liposome administration did not affect the severity of bacteremia or the survival of infected mice, these results imply that tissue macrophages have a major role in the production of both proinflammatory and anti-inflammatory cytokines in the circulation and in the causing septic physiology associated with P. aeruginosa pneumonia.
- Subjects :
- Male
Chemokine CXCL2
Pharmaceutical Science
Biology
Lung injury
medicine.disease_cause
Proinflammatory cytokine
Microbiology
Sepsis
Mice
Macrophages, Alveolar
medicine
Animals
Pseudomonas Infections
Mice, Inbred BALB C
Lung
medicine.diagnostic_test
Tumor Necrosis Factor-alpha
Septic shock
Pseudomonas aeruginosa
Macrophages
medicine.disease
Shock, Septic
Interleukin-10
Specific Pathogen-Free Organisms
Bronchoalveolar lavage
medicine.anatomical_structure
Bacteremia
Liposomes
Immunology
Chemokines
Clodronic Acid
Bronchoalveolar Lavage Fluid
Subjects
Details
- ISSN :
- 15322394 and 08982104
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Journal of Liposome Research
- Accession number :
- edsair.doi.dedup.....44ba5833aed5715c0ee4ab9f05910e6e