| Combined immunosuppressive and antibiotic therapy improves bacterial clearance and survival of polymicrobial septic peritonitis. | |
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MedLine Citation:
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PMID: 19487979 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Effective immunosuppressive therapy is essential to prevent transplant rejection but renders patients vulnerable to opportunistic infections. The present study investigates the effects of common immunosuppressive drugs on the course of septic peritonitis in an experimental mouse model. We show that treatment with a combination of tacrolimus, mycophenolate mofetil, and methylprednisolone resulted in highly elevated lethality of septic peritonitis. When immunosuppressive drugs were combined with antibiotic therapy, however, mice were almost completely protected. The combination of mycophenolate mofetil and methylprednisolone was shown to be required and sufficient to improve outcome of septic peritonitis in the presence of antibiotic therapy. Combined immunosuppressive and antibiotic therapy, but not antibiotic therapy alone, resulted in enhanced bacterial clearance. These beneficial effects were linked to an elevated expression of activation markers and an increased production of reactive oxygen metabolites by peritoneal neutrophils and correlated with a reduced messenger RNA expression of the inhibitory cytokine IL-22. In contrast, systemic or peritoneal levels of IL-10, IL-12, TNF-alpha, keratinocyte chemoattractant, and monocyte chemoattractant protein 1, and splenic messenger RNA levels of IFN-gamma were not influenced by the immunosuppressive therapy. These results therefore suggest that combined immunosuppressive and antibiotic therapy may improve bacterial clearance and survival of septic peritonitis by a mechanism that involves enhanced activation and antimicrobial activity of neutrophils and reduced production of IL-22. |
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Authors:
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Volker Assfalg; Norbert H?ser; Daniel Reim; Simone Kaiser-Moore; Tanja Rossmann-Bloeck; Heike Weighardt; Alexander R Novotny; Manfred J Stangl; Bernhard Holzmann; Klaus L Emmanuel |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 33 ISSN: 1540-0514 ISO Abbreviation: Shock Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-19 Completed Date: 2010-05-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 155-61 Citation Subset: IM |
Affiliation:
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Department of Surgery, Klinikum rechts der Isar, Technische Universit?t M?nchen, Munich, Germany. assfalg@chir.med.tu-muenchen.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Bacterial Agents / therapeutic use* Drug Therapy, Combination Female Flow Cytometry Immunosuppressive Agents / therapeutic use* Interleukin-10 / metabolism Interleukin-12 / metabolism Interleukins / metabolism Methylprednisolone / therapeutic use Mice Mice, Inbred C57BL Mycophenolic Acid / analogs & derivatives, therapeutic use Peritonitis / drug therapy*, microbiology* Reverse Transcriptase Polymerase Chain Reaction Sepsis / drug therapy*, metabolism, microbiology* Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Immunosuppressive Agents; 0/Interleukins; 0/Tumor Necrosis Factor-alpha; 0/interleukin-22; 128794-94-5/mycophenolate mofetil; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12; 24280-93-1/Mycophenolic Acid; 83-43-2/Methylprednisolone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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