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TITLE:  Biomarkers of inflammation in cattle determining the effectiveness of anti-inflammatory drugs
 
AUTHORS:  Myers MJ;Scott ML;Deaver CM;Farrell DE;Yancy HF;
 
YEAR:  2010
 
JOURNAL ABBREV:  J Vet Pharmacol Ther
 
MONTH:  Feb
 
TYPE:  JOUR
 
REFMAN INDEX:  548
 
JOURNAL FULL:  Journal of veterinary pharmacology and therapeutics
 
VOLUME:  33
 
ISSUE:  1
 
START PAGE:  1
 
END PAGE:  8
 
KEYWORDS:  blood;Cattle;CELLS;Commerce;CYCLOOXYGENASE-2 GENE;Dexamethasone;DIFFERENTIAL INHIBITION;EXPRESSION;Inflammation;INHIBITION;Lactation;LIPOPOLYSACCHARIDE;MESSENGER-RNA EXPRESSION;PROSTANOID BIOSYNTHESIS;RAT PERITONEAL-MACROPHAGES;SUPPRESSION;therapy;THROMBOXANE BIOSYNTHESIS;Tumor Necrosis Factor-alpha;WHOLE-BLOOD;
 
ABSTRACT:  The impact of nonsteroidal anti-inflammatory drugs (NSAID) on prostaglandin E-2 (PGE(2)) production and cyclooxygenase 2 (COX-2) mRNA expression in bovine whole blood (WB) cultures stimulated by lipopolysaccharide (LPS) was determined, using the blood from six Holstein dairy cattle in various stages of lactation. Peak production of PGE(2) occurred 24 h after LPS stimulation but did not result in detectable concentrations of thromboxane B-2 (TXB2). The NSAID indomethacin, aspirin, flunixin meglumine, and 4-[5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzene sulfonamide (PTPBS; celecoxib analogue), along with dexamethasone, were all equally effective in reducing the concentration of PGE(2) in the bovine WB culture supernatants. Bradykinin exhibited peak supernatant concentrations 1 h after LPS stimulation. Dexamethasone and the NSAID used in this study were equally effective at inhibiting bradykinin production. Peak induction of COX-2 mRNA occurred 3 h post-LPS stimulation. However, neither dexamethasone nor any of the NSAID used in this study altered COX-2 mRNA concentrations. In contrast, aspirin, flunixin meglumine, and PTPBS reduced tumor necrosis factor-alpha (TNF alpha) mRNA concentration. These results demonstrate that bovine blood cells respond to NSAID therapy like other mammalian cells with respect to inhibition of PGE(2) production and suppression of TNF mRNA induction, but do not inhibit induction of COX-2 mRNA
 
AFFILIATIONS:  US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA
 
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