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. 1985 Aug 1;162(2):401–412. doi: 10.1084/jem.162.2.401

Necrotic inflammatory reaction induced by muramyl dipeptide in guinea pigs sensitized by tubercle bacilli

PMCID: PMC2187735  PMID: 3926935

Abstract

In the course of studies aimed at determining whether MDP was antigenic or not, a hitherto unreported phenomenon was noticed. Injection (a provocative injection) of muramyl dipeptide (MDP) caused severe inflammation, with hemorrhage and necrosis in the footpads of guinea pigs, where tubercle bacilli in water-oil emulsion (a preparatory injection) had been injected 3-8 wk earlier. Sometimes the reaction was accompanied by generalized and fatal shock. Several related substances were tested, and only a combination of tubercle bacilli, or MDP plus proteins as the preparatory injection, and MDP as the provocative injection was found to induce this inflammatory necrotic reaction. Development of delayed hypersensitivity to protein antigens may be important for priming, but MDP and not the protein antigens provoked the reaction. This reaction was, so far, only observed in guinea pigs. Although this reaction appears to be similar to the Shwartzman reaction, the two reactions were found to differ from each other in several important points.

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Selected References

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  1. Audibert F., Heymer B., Gros C., Schleifer K. H., Seidl P. H., Chedid L. Absence of binding of MDP, a synthetic immunoadjuvant, to anti-peptidoglycan antibodies. J Immunol. 1978 Oct;121(4):1219–1222. [PubMed] [Google Scholar]
  2. Byars N. E. Two adjuvant-active muramyl dipeptide analogs induce differential production of lymphocyte-activating factor and a factor causing distress in guinea pigs. Infect Immun. 1984 May;44(2):344–350. doi: 10.1128/iai.44.2.344-350.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CLUFF L. E., BERTHRONG M. The inhibition of the local Shwartzman reaction by heparin. Bull Johns Hopkins Hosp. 1953 May;92(5):353–369. [PubMed] [Google Scholar]
  4. Chedid L., Audibert F., Johnson A. G. Biological activities of muramyl dipeptide, a synthetic glycopeptide analogous to bacterial immunoregulating agents. Prog Allergy. 1978;25:63–105. [PubMed] [Google Scholar]
  5. Emori K., Tanaka A. Granuloma formation by synthetic bacterial cell wall fragment: muramyl dipeptide. Infect Immun. 1978 Feb;19(2):613–620. doi: 10.1128/iai.19.2.613-620.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kotani S., Watanabe Y., Shimono T., Harada K., Shiba T. Correlation between the immunoadjuvant activities and pyrogenicities of synthetic N-acetylmuramyl-peptides or -amino acids. Biken J. 1976 Mar;19(1):9–13. [PubMed] [Google Scholar]
  7. Krueger J. M., Pappenheimer J. R., Karnovsky M. L. Sleep-promoting effects of muramyl peptides. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6102–6106. doi: 10.1073/pnas.79.19.6102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. McKAY D. G., MERRILL S. J., WEINER A. E., HERTIG A. T., REID D. E. The pathologic anatomy of eclampsia, bilateral renal cortical necrosis, pituitary necrosis, and other acute fatal complications of pregnancy, and its possible relationship to the generalized Shwartzman phenomenon. Am J Obstet Gynecol. 1953 Sep;66(3):507–539. doi: 10.1016/0002-9378(53)90068-4. [DOI] [PubMed] [Google Scholar]
  9. Nagao S., Tanaka A. Muramyl dipeptide-induced adjuvant arthritis. Infect Immun. 1980 May;28(2):624–626. doi: 10.1128/iai.28.2.624-626.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Nagao S., Tanaka A., Yamamoto Y., Koga T., Onoue K., Shiba T., Kusumoto K., Kotani S. Inhibition of macrophage migration by muramyl peptides. Infect Immun. 1979 May;24(2):308–312. doi: 10.1128/iai.24.2.308-312.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Parant M., Riveau G., Parant F., Dinarello C. A., Wolff S. M., Chedid L. Effect of indomethacin on increased resistance to bacterial infection and on febrile responses induced by muramyl dipeptide. J Infect Dis. 1980 Nov;142(5):708–715. doi: 10.1093/infdis/142.5.708. [DOI] [PubMed] [Google Scholar]
  12. Ribi E. E., Cantrell J. L., Von Eschen K. B., Schwartzman S. M. Enhancement of endotoxic shock by N-acetylmuramyl-L-alanyl-(L-seryl)-D-isoglutamine (muramyl dipeptide). Cancer Res. 1979 Nov;39(11):4756–4759. [PubMed] [Google Scholar]
  13. Riveau G., Masek K., Parant M., Chedid L. Central pyrogenic activity of muramyl dipeptide. J Exp Med. 1980 Oct 1;152(4):869–877. doi: 10.1084/jem.152.4.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Tanaka A., Emori K. Epithelioid granuloma formation by a synthetic bacterial cell wall component, muramyl dipeptide (MDP). Am J Pathol. 1980 Mar;98(3):733–748. [PMC free article] [PubMed] [Google Scholar]

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