title: Lipopolysaccharide-induced paw edema model for detection of cytokine modulating anti-inflammatory agents.
abstract: 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.affiliation: Inflammation Biology Laboratory, Dr. Reddy's Laboratories Ltd., Discovery Research SBU, Bollaram Road, Miyapur, Hyderabad 500049, India.
authors.forename: Bhargavi N L
authors.initials: BN
authors.lastname: Vajja
authors.forename: Suresh
authors.initials: S
authors.lastname: Juluri
authors.forename: Manju
authors.initials: M
authors.lastname: Kumari
authors.forename: Labonyamoy
authors.initials: L
authors.lastname: Kole
authors.forename: Ranjan
authors.initials: R
authors.lastname: Chakrabarti
authors.forename: Vishwas D
authors.initials: VD
authors.lastname: Joshi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan; D000068579:Celecoxib; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006614:Hindlimb; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D007783:Lactones / Q000494:pharmacology; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D015850:Interleukin-6; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C116926:rofecoxib; D002351:Carrageenan; D000068579:Celecoxib