Document Detail


Interferon-gamma inhibition attenuates lethality after cecal ligation and puncture in rats: implication of high mobility group box-1.
MedLine Citation:
PMID:  16205327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interferon (IFN)-gamma is an important immunomodulatory agent that is stimulated during infection to aid in host defense. However, increased IFN-gamma levels have been implicated as a mediator in various models of tissue injury and endotoxemia. We have previously shown that inhibition of IFN-gamma decreased bacterial load by accelerating peritoneal fibrin deposition in the cecal ligation and puncture (CLP) model of peritonitis. In addition, circulating inflammatory mediators such as interleukin (IL)-6 were reduced by IFN-gamma inhibition. In the present study, we show that administration of IFN-gamma antibody (1.2 mg/kg, i.v.) attenuated mortality after CLP. Administration of this antibody was able to reduce mortality when given immediately after CLP or 24 h after CLP surgery. Mortality in sepsis has been closely associated with increased release of high mobility group box-1 (HMGB1). Furthermore, it has been reported that IFN-gamma stimulates the release of HMGB1 from macrophages. Our studies showed that inhibition of IFN-gamma activity in vivo reduced the levels of HMGB1 in peritoneal fluid and serum of CLP rats 24 h after surgery. In addition, the decrease in HMGB1 was associated with an increase in tissue repair as evidenced by histological analyses. These results suggest that the attenuation of mortality in IFN-gamma antibody-treated rats was associated with a decrease in HMGB1 release.
Authors:
Kingsley Yin; Elizabeth Gribbin; Haichao Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  24     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-05     Completed Date:  2006-02-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  396-401     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, UMDNJ-School of Osteopathic Medicine, Stratford, New Jersey 08084, USA. yinki@umdni.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cecum / pathology
HMGB1 Protein / chemistry*
Inflammation
Interferon-gamma / antagonists & inhibitors*,  chemistry,  metabolism
Ligation
Male
Rats
Rats, Sprague-Dawley
Sepsis / drug therapy*,  mortality
Time Factors
Wound Healing
Chemical
Reg. No./Substance:
0/HMGB1 Protein; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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