Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1961 Jan 1;113(1):83–94. doi: 10.1084/jem.113.1.83

EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM

III. NITROGEN EXCRETION AFTER ACTH AS AN ASSAY FOR ENDOTOXIN

L Joe Berry 1, Dorothy S Smythe 1
PMCID: PMC2137337  PMID: 19867185

Abstract

There exists an inverse proportionality between number of heat-killed cells of Salmonella typhimurium injected intraperitoneally into mice and the quantity of urinary nitrogen the animals excrete during a 17 hour period following the subcutaneous administration of 2 units of ACTH. This relationship has been developed into an assay for bacterial endotoxin. Mice immunized against S. typhimurium require 10 to 20 times the number of cells needed by control animals to suppress urinary nitrogen excretion to the same extent. Intravenous saccharated iron oxide sensitizes animals so that fewer heat-killed salmonellae can be detected. Heat-killed cells of Staphylococcus aureus are without effect in the assay. Several lipopolysaccharides derived from Gram-negative bacteria are effective in preventing the rise of urinary nitrogen excreted in response to ACTH and the amount required, compared to the LD50, is in the same ratio for all of them. Citrated mouse serum partially inactivates the endotoxin during in vitro incubation for 1 hour at 37°C. while normal serum does not. Dichloroisoproterenol protects mice against the lethal effects of lipopolysaccharide and it lowers its effectiveness in the assay. The minimum amount of endotoxin reliably determined by the test is 0.25 µg. of an E. coli preparation that was given intravenously in mice in which the reticuloendothelial system had been "blocked" with saccharated iron oxide.

Full Text

The Full Text of this article is available as a PDF (651.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BENNETT I. L., Jr, CLUFF L. E. Bacterial pyrogens. Pharmacol Rev. 1957 Dec;9(4):427–479. [PubMed] [Google Scholar]
  2. BERRY L. J., SMYTHE D. S. Effect of bacterial endotoxin on metabolism. II Protein-carbohydrate balance following cortisone. Inhibition of intestinal absorption and adrenal response to ACTH. J Exp Med. 1959 Sep 1;110:407–418. doi: 10.1084/jem.110.3.407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BURROWS W. Endotoxins. Annu Rev Microbiol. 1951;5:181–196. doi: 10.1146/annurev.mi.05.100151.001145. [DOI] [PubMed] [Google Scholar]
  4. Beeson P. B., Technical Assistance of Elizabeth Roberts TOLERANCE TO BACTERIAL PYROGENS : II. ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM. J Exp Med. 1947 Jun 30;86(1):39–44. doi: 10.1084/jem.86.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. GOOD R. A., THOMAS L. Studies on the generalized Shwartzman reaction. II. The production of bilateral cortical necrosis of the kidneys by a single injection of bacterial toxin in rabbits previously treated with thorotrast or trypan blue. J Exp Med. 1952 Dec;96(6):625–641. doi: 10.1084/jem.96.6.625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. HALBERG F., HOWARD R. B. 24 Hour periodicity and experimental medicine examples and interpretations. Postgrad Med. 1958 Oct;24(4):349–358. doi: 10.1080/00325481.1958.11692235. [DOI] [PubMed] [Google Scholar]
  7. LANDY M., SKARNES R. C., ROSEN F. S., TRAPANI R. J., SHEAR M. J. Inactivation of biologically active endotoxic polysaccharides by fresh human serum. Proc Soc Exp Biol Med. 1957 Dec;96(3):744–747. doi: 10.3181/00379727-96-23596. [DOI] [PubMed] [Google Scholar]
  8. LANDY M., TRAPANI R. J., SHEAR M. J. Inactivation of endotoxin by a humoral component. IV. Alteration in the immunological properties of typhoid endotoxin. J Exp Med. 1959 Nov 1;110:731–750. doi: 10.1084/jem.110.5.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. MCLEAN R. A., BERRY L. J. Adrenergic inhibition and lethal effect of bacterial endotoxin in mice. Proc Soc Exp Biol Med. 1960 Oct;105:91–95. doi: 10.3181/00379727-105-26019. [DOI] [PubMed] [Google Scholar]
  10. MORAN N. C., PERKINS M. E. Adrenergic blockade of the mammalian heart by a dichloro analogue of isoproterenol. J Pharmacol Exp Ther. 1958 Nov;124(3):223–237. [PubMed] [Google Scholar]
  11. POWELL C. E., SLATER I. H. Blocking of inhibitory adrenergic receptors by a dichloro analog of isoproterenol. J Pharmacol Exp Ther. 1958 Apr;122(4):480–488. [PubMed] [Google Scholar]
  12. SKARNES R. C., ROSEN F. S., SHEAR M. J., LANDY M. Inactivation of endotoxin by a humoral component. II. Interaction of endotoxin with serum and plasma. J Exp Med. 1958 Nov 1;108(5):685–699. doi: 10.1084/jem.108.5.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. SMITH R. T., THOMAS L. Influence of age upon response to meningococcal endotoxin in rabbits. Proc Soc Exp Biol Med. 1954 Aug-Sep;86(4):806–809. doi: 10.3181/00379727-86-21239. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES