Document Detail


Lipopolysaccharide-induced paw edema model for detection of cytokine modulating anti-inflammatory agents.
MedLine Citation:
PMID:  15182729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytokines are critical to pathogenesis of inflammatory disorders. So inhibition of their action provides therapeutic benefits in various diseases. Although inhibition of inflammation caused by intraperitoneally administered LPS can identify cytokine modulators, this inflammatory test-agent does not allow one to determine overall anti-inflammatory potential. Functional characteristics of Carrageenan (Cara)-induced edema were valuable for identification of nonsteroidal anti-inflammatory drugs (NSAIDS). Hence, the potential of LPS-induced paw inflammation was investigated and compared to that by Cara. Stimulation of isolated rat peritoneal exudates cells (PEC) with 10 ng/ml LPS, but not Cara, induced IL-6 (3.04+/-0.2 ng/ml) and TNFalpha (1.030.09 ng/ml). At least 100 mg/ml Cara was necessary for detection of IL-6 (2.03+/-0.1 ng/ml) and TNFalpha (0.6+0.09 ng/ml) in PEC. Similar to Cara, subplantar administration of LPS-induced inflammatory paw edema in rats. LPS, but not Cara, induced TNFalpha (2.14+/-0.6 ng/ml) and IL-6 (2.9+/-0.5 ng/ml) in serum at 1 and 3 h, respectively, which returned to basal levels by 5 h. LPS-induced serum TNFalpha (sTNFalpha) levels closely paralleled paw swelling and its neutralization by anti-TNFalpha antibody or inhibition by pentoxifylline and nimesulide correlated with inhibition of inflammation. Similar to earlier reports, rofecoxib induced sTNFalpha at 30 mg/kg and exhibited pro-inflammatory effect by enhancing paw swelling. LPS-induced edema provides a useful functional model for identification of cytokine modulating anti-inflammatory agents.
Authors:
Bhargavi N L Vajja; Suresh Juluri; Manju Kumari; Labonyamoy Kole; Ranjan Chakrabarti; Vishwas D Joshi
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  International immunopharmacology     Volume:  4     ISSN:  1567-5769     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-08     Completed Date:  2005-02-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  901-9     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Elsevier B.V.
Affiliation:
Inflammation Biology Laboratory, Dr. Reddy's Laboratories Ltd., Discovery Research SBU, Bollaram Road, Miyapur, Hyderabad 500049, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*,  therapeutic use
Carrageenan
Cells, Cultured
Disease Models, Animal
Drug Evaluation, Preclinical / methods
Edema / chemically induced,  drug therapy,  immunology*
Female
Hindlimb
Interleukin-1 / biosynthesis,  blood
Interleukin-6 / biosynthesis,  blood
Lactones / pharmacology
Lipopolysaccharides
NF-kappa B / metabolism
Peritoneal Cavity / cytology
Pyrazoles / pharmacology
Rats
Rats, Wistar
Sulfonamides / pharmacology
Sulfones / pharmacology
Tumor Necrosis Factor-alpha / analysis,  antagonists & inhibitors,  biosynthesis*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Interleukin-1; 0/Interleukin-6; 0/Lactones; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Pyrazoles; 0/Sulfonamides; 0/Sulfones; 0/Tumor Necrosis Factor-alpha; 0/rofecoxib; 169590-42-5/celecoxib; 9000-07-1/Carrageenan

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