Document Detail


Interferon gamma increases sensitivity to endotoxin.
MedLine Citation:
PMID:  1908923     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interferon-gamma (IFN-gamma) has been proposed for use following severe trauma to reverse depressed macrophage (M phi) function and thereby reduce infection, sepsis, and subsequent multiple organ failure syndrome (MOFS). However, an excessive inflammatory response by M phi s and other components of the inflammatory cascade is thought to be central to the underlying pathophysiology of MOFS. Endotoxin (LPS) has been implicated as a principal mediator of sepsis-induced MOFS by stimulating M phi s and leukocytes (WBC). This study addresses the following question: Does IFN-gamma predispose normal rabbits to a pathophysiologic response to LPS infusion? Four groups of New Zealand White rabbits (n = 6, each group) were prepared for measurement of cardiac output, arterial pressure, arterial PO2, and WBC counts over a 6-hr period. Group I (control) was instrumented alone, Group II (LPS alone) was given a subclinical dose of 1.0 micrograms/kg of Escherichia coli LPS iv, Group III (IFN-gamma alone) was given recombinant rabbit IFN-gamma (5.0 micrograms/kg subcutaneous) for 3 days prior to preparation for measurements, and Group IV (IFN-gamma + LPS) received 3 days of IFN-gamma followed by LPS. One hour prior to sacrifice 5.0 microCi of 125I-albumin was given and bronchoalveolar lavage was performed at death to determine the lavage/plasma 125I ratio as an index of pulmonary permeability. The results indicate that IFN + LPS animals had significant decreases in cardiac output, PO2, and WBC counts, and increased lavage/plasma ratio of 125I-albumin when compared to all other groups (P less than 0.05 by ANOVA, t test). Neither LPS alone nor IFN-gamma alone had a significant effect on measured variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
G J Jurkovich; W J Mileski; R V Maier; R K Winn; C L Rice
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of surgical research     Volume:  51     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1991-10-03     Completed Date:  1991-10-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  197-203     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Washington School of Medicine, Harborview Medical Center, Seattle 98104.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arteries
Blood Pressure / drug effects
Capillary Permeability / drug effects
Cardiac Output / drug effects
Endotoxins / pharmacology*
Escherichia coli*
Interferon-gamma / pharmacology*
Leukocyte Count / drug effects
Lipopolysaccharides / pharmacology
Oxygen / blood
Pulmonary Circulation / drug effects
Rabbits
Grant Support
ID/Acronym/Agency:
GM 07037/GM/NIGMS NIH HHS; GM 42686/GM/NIGMS NIH HHS; HL 43141/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Lipopolysaccharides; 7782-44-7/Oxygen; 82115-62-6/Interferon-gamma

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