Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1966 Sep 1;124(3):461–482. doi: 10.1084/jem.124.3.461

INHIBITION OF THE SECONDARY ANTIBODY RESPONSE IN VITRO BY SALICYLATE AND GENTISATE

Charles Tesch Ambrose 1
PMCID: PMC2138239  PMID: 5922744

Abstract

Salicylate inhibition of the secondary antibody response initiated in vitro on day 0 has been studied in cultures of rabbit lymph node fragments. Levels of 1.25 to 1.5 mM (0.20 to 0.24 mg/ml) sodium salicylate present in serum-free medium throughout an 18- or 21-day culture period completely inhibit the secondary response. This inhibition is largely accomplished by the drug's action during the first 9 days, which corresponds to the inductive phase for this culture system. Relatively little inhibition is produced by adding the drug only after day 9, although over 90% of the antibody produced during a 21-day experiment is synthesized after day 9. Studies with media of different pH's show that this inhibition is more correctly a function of the nonionized salicylic acid concentration in the medium than of the total salicylate concentration. Arguments are presented against the possibility that salicylate at the levels used here inhibits antibody synthesis by uncoupling oxidative phosphorylation. Acetylsalicylic acid (aspirin) produces the same degree of inhibition in vitro as do equimolar concentrations of sodium salicylate. Gentisate (5-hydroxysalicylate) is 15-fold more effective in producing 50% inhibition than salicylate; its temporal pattern of inhibition is similar to that of salicylate.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. AMBROSE C. T., COONS A. H. Studies on antibody production. VIII. The inhibitory effect of chloramphenicol on the synthesis of antibody in tissue culture. J Exp Med. 1963 Jun 1;117:1075–1088. doi: 10.1084/jem.117.6.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. AMBROSE C. T. THE REQUIREMENT FOR HYDROCORTISONE IN ANTIBODY-FORMING TISSUE CULTIVATED IN SERUM-FREE MEDIUM. J Exp Med. 1964 Jan 1;119:1027–1049. doi: 10.1084/jem.119.6.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ambrose C. T. Symposium on in vitro studies of the immune response. 3. Biochemical agents affecting the inductive phase of the secondary antibody respose initiated in vitro. Bacteriol Rev. 1966 Jun;30(2):408–417. doi: 10.1128/br.30.2.408-417.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BATTERMAN R. C., KRYLE L. S., DANN S. The analgesic action of sodium gentisate. N Y State J Med. 1951 May 1;51(9):1152–1154. [PubMed] [Google Scholar]
  5. BATTERMAN R. C., SOMMER E. M. Fate of gentisic acid in man as influenced by alkalinization and acidification. Proc Soc Exp Biol Med. 1953 Mar;82(3):376–379. doi: 10.3181/00379727-82-20121. [DOI] [PubMed] [Google Scholar]
  6. BECKMAN H. Differential distribution of enzyme hydrolyzing acetylsalicylic acid (aspirin) in certain fluids of the rat. Proc Soc Exp Biol Med. 1956 Oct;93(1):144–146. doi: 10.3181/00379727-93-22689. [DOI] [PubMed] [Google Scholar]
  7. BRODY T. M. Action of sodium salicylate and related compounds on tissue metabolism in vitro. J Pharmacol Exp Ther. 1956 May;117(1):39–51. [PubMed] [Google Scholar]
  8. BUTLER W. T., COONS A. H. STUDIES ON ANTIBODY PRODUCTION. XII. INHIBITION OF PRIMING BY DRUGS. J Exp Med. 1964 Dec 1;120:1051–1060. doi: 10.1084/jem.120.6.1051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. CLARKE N. E., MOSHER R. E., CLARKE C. N. Phenolic compounds in the treatment of rheumatic fever. I. A study of gentisic acid derivatives. Circulation. 1953 Feb;7(2):247–257. doi: 10.1161/01.cir.7.2.247. [DOI] [PubMed] [Google Scholar]
  10. CRABTREE R. E., DATA J. B., CHRISTIAN J. E. A study of the oxidative metabolism of acetylsalicylic, salicylic, and gentisic acid in fevered animals. J Am Pharm Assoc Am Pharm Assoc. 1958 Aug;47(8):602–605. doi: 10.1002/jps.3030470821. [DOI] [PubMed] [Google Scholar]
  11. CRUCHAUD A., COONS A. H. STUDIES ON ANTIBODY PRODUCTION. 13. THE EFFECT OF CHLORAMPHENICOL ON PRIMING IN MICE. J Exp Med. 1964 Dec 1;120:1061–1074. doi: 10.1084/jem.120.6.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Coburn A. F., Kapp E. M. THE EFFECT OF SALICYLATES ON THE PRECIPITATION OF ANTIGEN WITH ANTIBODY. J Exp Med. 1943 Feb 1;77(2):173–183. doi: 10.1084/jem.77.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Derick C. L., Hitchcock C. H., Swift H. F. THE EFFECT OF ANTI-RHEUMATIC DRUGS ON THE ARTHRITIS AND IMMUNE BODY PRODUCTION IN SERUM DISEASE. J Clin Invest. 1928 Apr;5(3):427–440. doi: 10.1172/JCI100169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. FORMAN C., SEIFTER J., EHRICH W. E. Effects of salicylates and other drugs on experimental serum disease. J Allergy. 1949 Jul;20(4):273–285. doi: 10.1016/0021-8707(49)90041-6. [DOI] [PubMed] [Google Scholar]
  15. Lutwak-Mann C. The effect of salicylate and cinchophen on enzymes and metabolic processes. Biochem J. 1942 Dec;36(10-12):706–728. doi: 10.1042/bj0360706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lutwak-Mann C. The excretion of a metabolic product of salicylic acid. Biochem J. 1943 Jul;37(2):246–248. doi: 10.1042/bj0370246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. MICHAELIDES M. C., COONS A. H. Studies on antibody production. V. The secondary response in vitro. J Exp Med. 1963 Jun 1;117:1035–1051. doi: 10.1084/jem.117.6.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Meyer K., Ragan C. The Antirheumatic Effect of Sodium Gentisate. Science. 1948 Sep 10;108(2802):281–281. doi: 10.1126/science.108.2802.281. [DOI] [PubMed] [Google Scholar]
  19. PECCI J., FOYE W. O. The avidity of salicylic, gentisic, and salicyluric acids for heavy metal cations. J Am Pharm Assoc Am Pharm Assoc. 1960 Jul;49:411–414. doi: 10.1002/jps.3030490702. [DOI] [PubMed] [Google Scholar]
  20. Rantz L. A., Boisvert P. J., Spink W. W. Hemolytic Streptococcal Sore Throat: Antibody Response Following Treatment With Penicillin, Sulfadiazine, and Salicylates. Science. 1946 Mar 22;103(2673):352–353. doi: 10.1126/science.103.2673.352. [DOI] [PubMed] [Google Scholar]
  21. STAVITSKY A. B. Micromethods for the study of proteins and antibodies. I. Procedure and general applications of hemagglutination and hemagglutination-inhibition reactions with tannic acid and protein-treated red blood cells. J Immunol. 1954 May;72(5):360–367. [PubMed] [Google Scholar]
  22. Swift H. F. THE ACTION OF SODIUM SALICYLATE UPON THE FORMATION OF IMMUNE BODIES. J Exp Med. 1922 Nov 30;36(6):735–760. doi: 10.1084/jem.36.6.735. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES