Skip to main content
  • Published:

Reduced Response to Intravenous Endotoxin Injections Following Repeated Oral Administration of Endotoxin in the Pig

Abstract

Three prepubertal gilts were each given 100 mg of endotoxin (ET) in their ordinary feed rations, twice daily for 6 days; 3 other gilts received standard feed. Following ET feeding, all animals were injected intravenously (i.v.) with ET (1.0 µg/kg b.w.) once daily for 5 days. Blood samples were collected and analysed for hematology and total serum bile acids (S-BA), glutamate dehydrogenase (S-GLDH), calcium (S-Ca), iron (S-Fe), zinc (S-Zn) and a blood plasma metabolite (15-ketodihy-dro-PGF2a; P-PG) of prostaglandin F2a. The animals showed no apparent clinical symptoms following ET-feeding, neither did the blood analyses reveal effects of oral ET. However, when iv ET injections were given, the ET-fed animals showed fewer clinical signs of endotoxemia following the 2nd to 5th injection. S-BA and S-GLDH increased markedly in the standard-fed group following the first injection, while the ET-fed animals showed a much smaller increase in S-BA and no change in S-GLDH on that day. The difference in response may be explained by a direct uptake of ET from the gastrointestinal tract in the ET-fed pigs, making them less sensitive to the injected ET

References

  • Berczi I, Bertok L, Baintner K, Vereiss B: Failure of oral Escherichia coli endotoxin to induce either specific tolerance or toxic symptoms in rats. J. Path. Bact. 1968, 96, (481–486).

    Article  CAS  Google Scholar 

  • Bibby DC, Grimble RF: Effect of age on hypot–halamic Prostaglandin E2 production and fever in response to tumour necrosis factor (cachectin) and endotoxin in rats. Clin. Sei. 1991, 81, (313–317).

    CAS  Google Scholar 

  • Burrel R: Immunomodulation by bacterial endotoxin. Crit. Rev. Microbiol. 1990, 17, (189–208).

    Article  Google Scholar 

  • Cort N, Fredriksson G, Kindahl H, Edqvist L-E, Rylander R: A clinical and endocrine study on the effect of orally administered bacterial endotoxin in adult pigs and goats. J. vet. Med. 1990, A 37, 130–137.

    Article  CAS  Google Scholar 

  • Dinarello CA: Interleukin-1. Rev. Inf. Dis. 1984, 6, (51–95).

    Article  CAS  Google Scholar 

  • Deitch EA, Specian RD, Berg RD: Induction of early-phase tolerance to endotoxin-induced mucosal injury, xanthine oxidase activation, and bacterial translocation by pretreatment with endotoxin. Circ. Shock 1992, 36, (208–216).

    CAS  PubMed  Google Scholar 

  • Dobrowsky RT, Voyksner RD, Olson NC: Effect of SRI 63-675 on hemodynamics and blood PAF levels during porcine endotoxemia. Amer. J. Physiol. 1991, 260, (1455–1465).

    Google Scholar 

  • Erlinger S: Role of intracellular organelles in the hepatic transport of bile acids. Biomed. Pharma–cother. 1990, 44, (409–416).

    Article  CAS  Google Scholar 

  • Fox ES, Thomas P, Broitman SA: Hepatic mechanisms for clearance and detoxification of bacterial endotoxins. J. Nutr. Biochem. 1990, 1, 620–628.

    Article  CAS  Google Scholar 

  • Freudenberg Μ, Galanos C: The metabolic fate of endotoxins. In: Levin J, {etet al.} (eds). Progress in Clinical and Biological Research, Bacterial Endotoxins, Pathophysiological effects, Clinical Significance and Pharmacological Control. New York: Alan R. Liss Inc., 1988, 272, (63–75).

    CAS  Google Scholar 

  • Fruhman GJ: Endotoxins and leukocyte mobilization. J. Reticuloendothel. Soc. 1972, 12, (62–79).

    CAS  PubMed  Google Scholar 

  • Fujiki T, Kutsukake H, Imai K, Tanaka A: Protection of mice against bacterial infection by oral administration of bacterial lipopolysaccharide. Microbiol. Immunol. 1988, 32, (1253–1258).

    Article  CAS  Google Scholar 

  • Gans Η, Matsumoto Κ: Are enteric endotoxins able to escape from the intestine? Proc. Soc. exp. biol. Med. 1974, 147, (736–739).

  • Goodman ML, Way Β A, Irwin JW: The inflammatory response to endotoxin. J. Path. 1979, 128, (7–14).

    Article  CAS  Google Scholar 

  • Goto H, Rylander R: Kinetics of inhaled lipopolysaccharide in the guinea pig. J. Lab. Clin. Med. 1987, 110, (287–291).

    CAS  PubMed  Google Scholar 

  • Greisman SE: Induction of endotoxin tolerance. In: Nowotny A (ed). Beneficial effects of endotoxins. New York: Plenum Press, 1983, 149–178.

    Chapter  Google Scholar 

  • Härtung Τ, Wendel A: Endotoxin–inducible cytotoxi–city in liver cell cultures. II: Demonstration of endotoxin tolerance. Biochem. Pharmacol. 1992, 43, (191–196).

    Article  Google Scholar 

  • Holst H, Edqvist L-E, Kindahl H, Rylander R: Effects of oral and intravenous administration of endotoxin in prepubertal gilts. J. vet. Med. 1993, A40, 33–44.

    Article  Google Scholar 

  • Huber TL, Peed MC, Wilson RC, Goetsch DD: Endotoxin absorption in hay–fed and lactic acidotic sheep. Amer. J. vet. Res. 1979, 40, (792–794).

    CAS  PubMed  Google Scholar 

  • Hyldgaard-Jensen J, Palludan B, Panic B, Valenta M: Plasma enzymes of hepatic origin. Årsskr. K. Vet.-Landbohöjsk. 1969, 117–140.

    Google Scholar 

  • Kroker R, Römer C: The significance of serum bile acid concentrations as indicator of hepatic dysfunction in the mini-pig. Zbl. Vet. Med. 1984, A31, 287–295.

    Google Scholar 

  • Lang CH, Spitzer JA: Glucose kinetics and development of endotoxin tolerance during long–term continuous endotoxin infusion. Metabolism. 1987, 36, (469–474).

    Article  CAS  Google Scholar 

  • Markowitz ME, Rose JF, Mizruchi M: Circadian variations in serum zinc (Zn) concentrations: correlations with blood ionized calcium, serum total calcium and phosphate in humans. Amer. J. clin. Nutr. 1985, 41, (689–696).

    Article  CAS  Google Scholar 

  • Nolan JP: The role of intestinal endotoxins in gastrointestinal and liver diseases. In: Levin J, {etet al.} (eds): Progress in Clinical and Biological Research, Bacterial Endotoxins; Pathophysiological effects, Clinical Significance and Pharmacological Control. New York: Alan R. Liss Inc., 1988, 272, (147–159).

    CAS  Google Scholar 

  • Portolés Μ Τ, Ainaga MJ, Municio AM, Pagani R: Intracellular calcium and pH alterations induced by Escherichia coli endotoxin in rat hepatocytes. Biochim. Biophys. Acta Mol. Cell. Res. 1991, 1092, (1–6).

    Article  Google Scholar 

  • Ravin HA, Rowley D, Jenkins C, Fine J: On the absorption of bacterial endotoxin from the gastrointestinal tract of the normal and shocked animal. J. Exp. Med. 1960, 112, (783–792).

    Article  CAS  Google Scholar 

  • de Rodriguez Turco EB, Spitzer JA: Eicosanoid production in nonparenchymal liver cells isolated from rats infused with E. coli endotoxin. J. Leukocyte Biol. 1990, 48, (488–494).

    Article  Google Scholar 

  • Rodriguez H, Kunavongkrit A: Chronical venous catheterization for frequent blood sampling in unrestrained pigs. Acta vet. scand. 1983, 24, 318–320.

    Article  CAS  Google Scholar 

  • Rylander R: Dept. of Environmental Medicine, University of Gothenburg, Gothenburg, Sweden. 1989. (Unpublished observation).

    Google Scholar 

  • Sanchez-Cantu L, Rode HN, Christou N: Endotoxin tolerance is associated with reduced secretion of tumor necrosis factor. Arch. Surg. 1989, 124, (1432–1435).

    Article  CAS  Google Scholar 

  • Spitzer JA, Deaciuc IV: Prostaglandin F stimulates gluconeogenesis in the perfused rat liver and this effect is blunted in livers from endotoxin infused rats. Agents. Actions 1990, 31, (341–344).

    Article  CAS  Google Scholar 

  • Stewart GA, Clarkson GT: Serum iron and iron binding capacity in the horse. Victorian Veterinary Proceedings 1969, 27, (25–26).

  • Tracey JD, Jensen AH, Allhands RV: Bile acid metabolism in the pig. Cornell Vet. 1986, 76, (128–138).

    Google Scholar 

  • Truszczynski M, Pilaszek J: Effects of injection of enterotoxin, endotoxin or live culture of Escherichia coli into the small intestine of pigs. Res. vet. Sei. 1969, 10, (469–476).

    Article  CAS  Google Scholar 

  • Utili R, Abernathy CO, Zimmerman HJ: Cholestatic effects of Escherichia coli endotoxin on the isolated perfused rat liver. Gastroenterology 1976, 70, (248–253).

    Article  CAS  Google Scholar 

  • Vogel SN, Douches SD, Kaufman EN, Neta R: Induction of colony stimulating factor in vivo by recombinant interleukin la and recombinant tumor necrosis factor a. J. Immunol. 1987, 138, (2143–2148).

    CAS  PubMed  Google Scholar 

  • Wessels BC, Gaffin SL, Wells MT: Circulating plasma endotoxin (lipopolysaccharide) concentrations in healthy and hemorrhagic enteric dogs: antiendotoxin immunotherapy in hemorrhagic enteric endotoxemia. J. Amer. Anim. Hosp. Assoc. 1987, 23, (291–295).

    Google Scholar 

  • Wray C, Thomlinson JR: The effects of Escherichia coli endotoxin in calves. Res. vet. Sei. 1972, 13, (546–553).

    Article  CAS  Google Scholar 

  • Yagoda C, Bylund-Fellenius A-C, Kindahl Η: Clinical and endocrine response to repeated daily administration of endotoxin in pigs. Acta vet. scand. 1988, 29, (267–269).

    CAS  PubMed  Google Scholar 

  • Zuckerman SH, Evans GF, Butler LD: Endotoxin tolerance: independent regulation of inter–leukin-1 and tumor necrosis factor expression. Infect. Immun. 1991, 59, (2774–2780).

    Article  CAS  Google Scholar 

Download references

Acknowledgement

The present study was supported by the Swedish Council for Forestry and Agricultural Research, and the Farmers Research Council for Information and Development. We thank Dr C. Hard af Segerstad and Dr J. Holmdahl for their help with the histopathological and parasitological examinations, respectively.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holst, H., Edqvist, LE. & Kindahl, H. Reduced Response to Intravenous Endotoxin Injections Following Repeated Oral Administration of Endotoxin in the Pig. Acta Vet Scand 34, 405–419 (1993). https://doi.org/10.1186/BF03548185

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1186/BF03548185

Keywords