Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1977 Aug;17(2):325–329. doi: 10.1128/iai.17.2.325-329.1977

Enhanced susceptibility of mice to combinations of delta 9-tetrahydrocannabinol and live or killed gram-negative bacteria.

S G Bradley, A E Munson, W L Dewey, L S Harris
PMCID: PMC421122  PMID: 330405

Abstract

Combinations of delta 9-tetrahydrocannabinol (delta 9-THC) and bacterial endotoxin were shown to be hyperadditively toxic for mice. A variety of purified lipopolysaccharide (LPS) preparations elicted enhanced mortality in combination with delta 9-THC. Escherichia coli O26:B6 LPS (Boivin preparation) at an essentially nonlethal dose of 2.5 mg/kg reduced the dose of delta 9-THC required to kill 50% of the treated mice from ca. 350 to 150 mg/kg. Inbred BALB, DBA, and C3H/HeCr mice, noninbred ICR mice, and hybrid CDF1 and BDF1 mice were hyperreactive to combinations of delta 9-THC and LPS. Moreover, a variety of heat-killed intestinal and gram-negative bacteria, live E. coli, and complexes of lipid A with a variety of proteins substituted for LPS in the synergistic toxicity of LPS and delta 9-THC. Extracts of marijuana also elicited hyperreactivity to LPS. The hyperadditive lethality of combinations of delta 9-THC and LPS was markedly less in mice rendered refractory to LPS or delta 9-THC by repeated administration of LPS or delta 9-THC, respectively.

Full text

PDF
325

Selected References

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

  1. ATWOOD R. P., KASS E. H. RELATIONSHIP OF BODY TEMPERATURE TO THE LETHAL ACTION OF BACTERIAL ENDOTOXIN. J Clin Invest. 1964 Feb;43:151–169. doi: 10.1172/JCI104899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradley S. G., Adams A. C., Smith M. C. Potentiation of the toxicity of mithramycin by bacterial lipopolysaccharide. Antimicrob Agents Chemother. 1975 Mar;7(3):322–327. doi: 10.1128/aac.7.3.322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bradley S. G. Endotoxic activity of complexes of myristic acid and proteins. Proc Soc Exp Biol Med. 1976 Feb;151(2):267–270. doi: 10.3181/00379727-151-39189. [DOI] [PubMed] [Google Scholar]
  4. Bradley S. G., Marecki N. M., Bond J. S., Munson A. E., John D. T. Enhanced cytotoxicity in mice of combinations of concanavalin A and selected antitumor drugs. Adv Exp Med Biol. 1975;55:291–307. doi: 10.1007/978-1-4684-0949-9_16. [DOI] [PubMed] [Google Scholar]
  5. Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [DOI] [PubMed] [Google Scholar]
  6. Galanos C., Rietschel E. T., Lüderitz O., Westphal O., Kim Y. B., Watson D. W. Biological activities of lipid A complexed with bovine-serum albumin. Eur J Biochem. 1972 Dec 4;31(2):230–233. doi: 10.1111/j.1432-1033.1972.tb02524.x. [DOI] [PubMed] [Google Scholar]
  7. Hylemon P. B., Phibbs P. V., Jr Evidence against the presence of cyclic AMP and related enzymes in selected strains of Bacteroides fragilis. Biochem Biophys Res Commun. 1974 Sep 9;60(1):88–95. doi: 10.1016/0006-291x(74)90176-4. [DOI] [PubMed] [Google Scholar]
  8. Klausner H. A., Dingell J. V. The metabolism and excretion of delta 9-tetrahydrocannabinol in the rat. Life Sci I. 1971 Jan 1;10(1):49–59. doi: 10.1016/0024-3205(71)90245-1. [DOI] [PubMed] [Google Scholar]
  9. Marecki N. M., Bradley S. G., Munson A. E., Drummond D. C. Effect of bacterial lipopolysaccharide, lipid A, and concanavalin A on lethality of 5-fluorouracil for mice. Toxicol Appl Pharmacol. 1975 Jan;31(1):83–89. doi: 10.1016/0041-008x(75)90054-x. [DOI] [PubMed] [Google Scholar]
  10. Moore W. E., Holdeman L. V. Human fecal flora: the normal flora of 20 Japanese-Hawaiians. Appl Microbiol. 1974 May;27(5):961–979. doi: 10.1128/am.27.5.961-979.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nahas G. G., Suciu-Foca N., Armand J. P., Morishima A. Inhibition of cellular mediated immunity in marihuana smokers. Science. 1974 Feb 1;183(4123):419–420. doi: 10.1126/science.183.4123.419. [DOI] [PubMed] [Google Scholar]
  12. Rose W. C., Bradley S. G., Lee I. P. Enhanced toxicity for mice of vincristine and other chemotherapeutic agents with Salmonella typhosa endotoxin and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1972 Jun;1(6):489–495. doi: 10.1128/aac.1.6.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rose W. C. Interaction of bacterial toxins in the toxicity of chemotherapeutic agents. CRC Crit Rev Toxicol. 1973 Sep;2(2):159–209. doi: 10.3109/10408447309025702. [DOI] [PubMed] [Google Scholar]
  14. WARAVDEKAR V. S., SASLAW L. D. A sensitive colorimetric method for the estimation of 2-deoxy sugars with the use of the malonaldehyde-thiobarbituric acid reaction. J Biol Chem. 1959 Aug;234(8):1945–1950. [PubMed] [Google Scholar]
  15. Wilkins T. D., Chalgren S. Medium for use in antibiotic susceptibility testing of anaerobic bacteria. Antimicrob Agents Chemother. 1976 Dec;10(6):926–928. doi: 10.1128/aac.10.6.926. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES