Document Detail


Therapeutic potential for transient inhibition of adenosine deaminase in systemic inflammatory response syndrome.
MedLine Citation:
PMID:  12771621     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: We sought to determine the potential usefulness of 2'-deoxycoformycin (pentostatin), an inhibitor of adenosine deaminase, as a postinsult, or prophylactic treatment for systemic inflammatory response syndrome resulting from fecal peritonitis. DESIGN: Prospective, randomized, controlled experiment. SETTING: Small animal basic science laboratory. SUBJECTS: Male Spague-Dawley rats, weighing 300 to 350 g. INTERVENTIONS: Rats with fecal peritonitis (intraperitoneal cecal slurry) were treated with 1 mg/kg pentostatin intraperitoneally 24 hrs before, or intravenously when signs of illness presented (2 hrs after induction of peritonitis). Signs of illness included tachycardia, tachypnea, and leukopenia. All rats received 50 mL/kg 0.9% saline resuscitative fluid at 2 hrs. MEASUREMENTS AND MAIN RESULTS: Survival to day 6 was 100% in nonseptic sham rats, but 33% in untreated septic rats. In rats given pentostatin either 2 hrs after the insult, or 24 hrs before the insult, 6-day survival improved to 81% and 78%, respectively. Histology revealed diffuse peritonitis, and evidence of systemic inflammatory response syndrome, including local and distant site vascular damage and leukocyte activation. These responses to the septic challenge were abrogated by pentostatin treatment. Return of significant amount of tissue adenosine deaminase activity by 24 hrs and later recovery of white blood cell counts argue against any potential for inappropriate immunosuppression by pentostatin. CONCLUSIONS: These data indicate that the novel use of pentostatin to prevent systemic inflammatory response syndrome secondary to fecal peritonitis shows uncommon promise as a therapeutic tool. All indices of systemic inflammatory response syndrome were abrogated and survival improved when pentostatin was not given until after signs of the illness became manifest. Because protection was afforded with treatment 24 hrs in advance of the inciting insult, pentostatin also has the unique potential for use as a true prophylactic agent.
Authors:
William R Law; Victor E Valli; Beth A Conlon
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Critical care medicine     Volume:  31     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-28     Completed Date:  2003-06-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1475-81     Citation Subset:  AIM; IM    
Affiliation:
University of Illinois, College of Medicine at Chicago, 60612, USA. wrlaw@uic.edu
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MeSH Terms
Descriptor/Qualifier:
Adenosine Deaminase / analysis,  antagonists & inhibitors*,  immunology
Animals
Disease Models, Animal*
Drug Evaluation, Preclinical
Feces
Immunosuppressive Agents / pharmacology,  therapeutic use*
Infusions, Intravenous
Injections, Intraperitoneal
Leukocyte Count
Male
Pentostatin / pharmacology,  therapeutic use*
Peritonitis / complications
Proportional Hazards Models
Prospective Studies
Random Allocation
Rats
Rats, Sprague-Dawley
Survival Analysis
Systemic Inflammatory Response Syndrome / drug therapy*,  enzymology,  microbiology,  mortality,  prevention & control*
Time Factors
Grant Support
ID/Acronym/Agency:
R41 GM065593/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 53910-25-1/Pentostatin; EC 3.5.4.4/Adenosine Deaminase

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


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