The Influence of Flunixin on the Response to Salmonella typhimurium Endotoxin in Calves
Inverkan av flunixin på svaret på Salmonella typhimurium endotoxin hos kalv
Acta Veterinaria Scandinavica volume 30, pages 295–300 (1989)
Abstract
The effects of intravenous injection of 0.5 μg/kg body weight of Salmonella typhimurium endotoxin were studied in calves. The injection was followed by ruminai stasis and general dullness. The clinical signs disappeared within 24 hours.
The injection was followed by a tremendous increase in the plasma level of 15-ketodihydro-PGF2α, the main metabolite of PGF2α. The injection was also associated with a profound leukopenia and significant decreases in the serum levels of iron, zinc and calcium. In order to study the role of prostaglandin (PG) for the development of endotoxin-induced changes a group of calves was pretreated with flunixin, a potent cyclo-oxygenase inhibitor, at a dose of 2.2 mg/kg body weight. Flunixin inhibited the PG release completely, but did not influence the other responses to endotoxin.
The pyrogenic response to endotoxin was very moderate and it was suggested that fever is not the most suitable parameter for monitoring endotoxin effects in calves. The studied blood parameters (15-ketodihydro-PGF2α, iron, zinc, calcium and the number of leukocytes) appeared to be much more sensitive.
Sammenfattning
Effekterna av intravenös injektion av endotoxin från Salmonella typhimurium i dosen 0.5 μg/kg kroppsvikt studerades hos kalv. Injektionen följdes av mycket tydliga kliniska symtom. Kalvarna visade tecken på reducerad förmagsmotorik och kraftigt stört allmäntillstånd. De kliniska symtomen försvann dock inom 24 timmar.
Plasmakoncentrationen av 15-ketodihydro-PGF2α steg mycket påtagligt efter endotoxininjektionen. Vidare uppkom en mycket drastisk sänkning av antalet cirkulerande leukocyter och signifikanta sänkningar av serumkoncentrationerna av järn, zink och kalcium. För att studera vilken roll PG-frisätt ningen har för uppkomsten av de observerade blodkemiska förändringarna förbehandlades en grupp kalvar med flunixin, en potent PG synteshämmare. Flunixin blockerade frisättningen av PG fullständigt, men var helt utan effekt på övriga endotoxininducerade förändringar. Endotoxin gav ett myckel måttligt py-rogensvar och det konkluderades att de känsligaste parametrarna för att studera endotoxineffekter hos kalv är antalet leukocyter och koncentrationerna av 15-ketodihydro-PGF2α, järn, zink och kalcium.
References
Beisei RW: Magnitude of the host nutritional responses to infection. Amer. J. clin. Nutr. 1977, 30, 1236–1247.
Bernheim HA: Temperature regulation and fever. In: The Reticuloendothelial System. A. Comprehensive Treatise. Ed. Reichard SM and Filkins OP. Plenum Press, New York, 1985.
Depelchin Bo, Blöden S, Hooremans M, Noirfalise A, Ansay M: Clinical and experimental modifications of plasma iron and zinc concentrations in cattle. Vet. Rec. 1985, 116, 519–521.
Dinarello CA: Molecular mechanisms in endotoxin fever. Agents and Actions, 1983, 13, 470–485.
Fredriksson G: Prostaglandins, endotoxins and uterine bacteriology in reproduction of the doe and cow. Thesis, Uppsala, 1984.
Granström E, Kindahi H: Radioimmunoassay of the major plasma metabolite of PGF2 (X, 15-keto-13, 14-dihydro PGF2a. Methods Enzymol. 1982, 86, 320–339.
Griel LC, Zarkower A, Eberhart RJ: Clinical and cli- nicopathological effects of Eschericia coli endotoxin in mature cattle. Can. J. comp. Med. 1975, 39, 1–6.
Hardee GE, Smith JA, Harris SJ: Pharmacokinetics of fhmixin meglumine in the cow. Res. vet. Sci. 1985, 39, 110–112.
Luthman J, Jacobsson SO, Kindahi H: Influence of prostaglandins on calcium homeostasis in dairy cows. Zbl. Vet. Med. A, 1983, 30, 521–529.
Luthman J, Kindahi H, Jacobsson SO, Thunberg L: Local and general effects of Salmonella typhimu- rium endotoxin in calves. J. vet. med. A, 1988, 35, 586–595.
MacGregor RR: Granulocyte adherence changes induced by hemodialysis, endotoxin, epinephrine, and glucocorticoids. Ann. int. Med. 1977, 86, 35–39.
Margolis JH, Bottoms GD, Fessler JH: The efficacy of dexamethasone and flunixin meglumine in treating endotoxininduced changes in calves. Vet. Res. Comm. 1987, 11, 479–491.
Milton AS: Prostaglandins and fever. Trends in Pharmacol. Sei. 1982, 3, 490–492.
Mitchell RH, Kampschmidt RF: Leukocytic endogenous mediator in non-specific host defences. In: The Reticuloendothelial System. A Comprehensive treatise. Ed. Reichard SM, Filkins JP. Plenum Press, New York 1985.
Oppenheim JJ, Konvacs EJ, Matsushima K, Durim SK: There is more than one interleukin - 1. Immunology Today. 1986, 7, 45–56.
Pekarek RS, Beisel WR: Characterization of the endogenous mediators of serum zinc and iron depression during infection and other stresses. Proc. Soc. exp. Biol. Med. 1971, 138, 728–732.
Sankari S, Pekkanen T: The effect of endotoxin on the liver lipid peroxide levels and on the liver and plasma zinc concentrations in rats. Acta vet. scand. 1982, 23, 24–29.
Schrauwen E, Vandeplasche G, Laekman G, Houvenaghel A: Endotoxic shock in the piglet: Beneficial effects of prostaglandin synthesis inhibitors. Prostaglandins Leukotrienes and Medicine 1984, 73, 271–278.
Van Miert ASJPAM, Van Duin CTM, Verheijden JHM, Schotman AJH: Endotoxin-induced fever and associated haematological and blood biochemical changes in the goat: The effect of repeated administration and the influence of flurbiprofen. Res. Vet. Sei. 1982, 33, 248–255.
Van Miert ASJPAM: Fever and associated clinical and blood biochemical changes in the goat and other animal species. Vet. Quart. 1985, 7, 200–216.
Van Miert ASJPAM: Fever, anorexia and forestomach hypomotility in ruminants. Vet. Red. Comm. 1987, 77, 407–422.
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Luthman, J., Kindahl, H. & Jacobsson, S.O. The Influence of Flunixin on the Response to Salmonella typhimurium Endotoxin in Calves. Acta Vet Scand 30, 295–300 (1989). https://doi.org/10.1186/BF03548034
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DOI: https://doi.org/10.1186/BF03548034
Keywords
- leukopenia
- calcium
- iron
- zinc
- prostaglandin