Effect of LPS on Nonspecific Resistance to Bacterial Infections

  • Monique Parant


Bacterial endotoxins may affect the pathogenicity of a wide variety of infectious agents, not only gram-negative and gram-positive bacteria, but also fungi, parasites, and viruses. Originally demonstrated by Rowley (1956) using bacterial cell walls, and shortly later by several workers with partially purified endotoxins (Landy and Pillemer, 1956; Dubos and Schaedler, 1956), this capacity to nonspecifically enhance the host’s resistance to a bacterial infection created more excitement about these substances (reviewed in Cluff, 1971). Subsequently, during the 1960s, chemical and physical methods of modifying these complex toxins without destroying their protective properties were developed (reviewed in Sultzer, 1971). A significant but transient increase in resistance to infection has been observed when endotoxin is given several hours before initiation of infection, and very low doses of endotoxin were found to be effective (see Cluff, 1971). However, depending upon the dose and route of administration, and upon the time interval prior to the infectious challenge, a transient increase in susceptibility to infection was also reported in the first papers (Rowley, 1956; Landy and Pillemer, 1956; Dubos and Schaedler, 1956). This negative phase has been produced when endotoxin is injected at the time of challenge or shortly thereafter.


Bacterial Infection Bone Marrow Cell Mouse Strain Bacterial Endotoxin Phthalic Anhydride 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Auerbach, R., 1978, Ontogeny of immune responsiveness in the absence of the spleen: a review, in: Developmental and Comparative Immunology Vol. 2, pp. 219–228, Pergamon Press, Elmsford, N.Y.Google Scholar
  2. Beeson, P. B., 1947a, Tolerance to bacterial pyrogens. I. Factors influencing its development,J. Exp. Med. 86:29.PubMedCrossRefGoogle Scholar
  3. Beeson, P. B., 1947b, Tolerance to bacterial pyrogens. II. Role of the reticuloendothelial system,J. Exp. Med. 86:39.PubMedCrossRefGoogle Scholar
  4. Behling, U. H., and Nowotny, A., 1977, Immune adjuvancy of lipopolysaccharide and a non-toxic hydrolytic product demonstrating oscillating effects with time,J. Immunol. 118:1905.PubMedGoogle Scholar
  5. Berry, L.J., 1977, Bacterial toxins, CRC Crit. Rev. Toxicol. 1977:239.CrossRefGoogle Scholar
  6. Bianco, C., and Edelson, P. J., 1977, Macrophage activation in C3H/HeJ mice, Fed. Proc. 36:1263.Google Scholar
  7. Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., and Williamson, B., 1975, An endotoxin-induced serum factor that causes necrosis of tumors, Proc. Natl. Acad. Sci. USA 72:3666.PubMedCrossRefGoogle Scholar
  8. Chedid, L., and Parant, M., 1971, Hypersensitivity and tolerance to endotoxins, in: Microbial Toxins, Vol. V (S. Kadis, G. Weinbaum, and S.J. Ajl, eds.), pp. 415–459, Academic Press, New York.Google Scholar
  9. Chedid, L., Audibert, F., Bona, C., Damais, C., Parant, F., and Parant, M., 1975, Biological activities of endotoxins detoxified by alkylation, Infect. Immun. 12:714.PubMedGoogle Scholar
  10. Chedid, L., Parant, M., Damais, C., Parant, F., Juy, D., and Galelli, A., 1976, Failure of endotoxin to increase nonspecific resistance to infection of lipopolysaccharide low-responder mice, Infect. Immun. 13:722.PubMedGoogle Scholar
  11. Cluff, L. E., 1971, Effects of lipopolysaccharides (endotoxins) on susceptibility to infections, in: Microbial Toxins, Vol. V (S. Kadis, G. Weinbaum, and S.J. Ajl, eds.), pp. 399–413, Academic Press, New York.Google Scholar
  12. Coutinho, A., 1976, Genetic control of B-cell responses. I. Identification of the spleen B-cell defect in C3H/HeJ mice, Scand. J. Immunol. 5:129.PubMedCrossRefGoogle Scholar
  13. Dubos, R. J., and Schaedler, R. W., 1956, Reversible changes in the susceptibility of mice to bacterial infections,J. Exp. Med. 104:53.PubMedCrossRefGoogle Scholar
  14. Elin, R. J., Wolff, S. M., McAdam, K. P. W. J., Chedid, L., Audibert, F., Bernard, G., and Oberling, F., Properties of reference Escherichia coli endotoxin and its phthalylated derivative in humans, J. Infect. Dis. 144:329.Google Scholar
  15. Frccdman, H. H., 1960, Passive transfer of tolerance to pyrogenicity of bacterial endotoxin,J. Exp. Med. 111:453.CrossRefGoogle Scholar
  16. Galanos, C., 1975, Physical state and biological activity of lipopolysaccharides, toxicity and immunogenicity of the lipid A component, Z. Immunitaetsforsch. 149:214.Google Scholar
  17. Galelli, A., LeGarrec, Y., and Chedid, L., 1979, Transfer by bone marrow cells of increased natural resistance to Klebsiella pneumoniae induced by lipopolysaccharide in genetically deficient C3H/HeJ mice, Infect. Immun. 23:232.PubMedGoogle Scholar
  18. Glode, L. M., Mergenhagen, S. E., and Rosenstreich, D. L., 1976a, Significant contribution of spleen cells in mediating the lethal effects of endotoxin in vivo, Infect. Immun. 14:626.Google Scholar
  19. Glode, L. M., Scher, I., Osborne, B., and Rosenstreich, D. L., 1976b, Cellular mechanism of endotoxin unresponsiveness in C3H/HcJ mice,J. Immunol. 116:454.PubMedGoogle Scholar
  20. Glode, L. M., Jacques, A., Mergenhagen, S. E., and Rosenstreich, D. L., 1977, Resistance of macrophages from C3H/HeJ mice to the in vitro cytotoxic effects of endotoxin,J. Immunol. 119:162.PubMedGoogle Scholar
  21. Heppner, G., and Weiss, D. W., 1965, High susceptibility of strain A mice to endotoxin and endotoxin-red blood cell mixtures,J. Bacteriol. 90:696.PubMedGoogle Scholar
  22. Hoffman, M., Oettgen, H., Old, L., Mittler, R., and Hämmerling, U., 1978, Induction and immunological properties of tumor necrosis factor,J. Reticuloendothelial Soc. 23:307.Google Scholar
  23. Kampschmidt, R. F., and Pulliam, L. A., 1975, Stimulation of antimicrobial activity in the rat with leukocytic endogenous mediator,J. Reticuloendothelial Soc. 17:162.Google Scholar
  24. Kull, F. G., and Cuatrecasas, P., 1981, Preliminary characterization of the tumor cell cyto-toxin in tumor necrosis serum,J. Immunol. 126:1279.PubMedGoogle Scholar
  25. Landy, M., and Pillemer, L., 1956, Increased resistance to infection and accompanying alteration in properdin levels following administration of bacterial lipopolysaccharides,J. Exp. Med. 104:383.PubMedCrossRefGoogle Scholar
  26. Lüderitz, O., 1977, Endotoxins and other cell wall components of gram-negative bacteria and their biological activities, in: Microbiology 1977 (D. Schlessinger, ed.), pp. 239–246, American Society for Microbiology, Washington, D.C.Google Scholar
  27. McGhee, J. R., Michalek, S. M., Moore, R. N., Mergenhagen, S. E., and Rosenstreich, D. L., 1979, Genetic control of in vivo sensitivity to lipopolysaccharide: Evidence for co-dominant inheritance,J. Immunol. 122:2052.PubMedGoogle Scholar
  28. McIntire, F. C., Hargie, M. P., Schenck, J. R., Finley, R. A., Sievert, H. W., Rietschel, E. T., and Rosenstreich, D. L., 1976, Biologic properties of nontoxic derivatives of a lipopolysaccharide from Escherichia coli K235,J. Immunol. 117:674.PubMedGoogle Scholar
  29. Männel, D. N., Rosenstreich, D. L., and Mergenhagen, S. E., 1979, Mechanism of lipo-polysaccharide-induced tumor necrosis: Requirement for lipopolysaccharide-sensitive lymphoreticular cells, Infect. Immun. 24:573.PubMedGoogle Scholar
  30. Männel, D. N., Farrar, J. J., and Mergenhagen, S. E., 1980, Separation of a serum-derived tumoricidal factor from a helper factor for plaque-forming cells,J. Immunol. 124:1106.PubMedGoogle Scholar
  31. Milner, K. C., Rudbach, J. A., and Ribi, E., 1971, General characteristics of endotoxin, in: Microbial Toxins, Vol. V (S. Kadis, G. Weinbaum, and S. J. Ajl, eds.), pp. 1–66, Academic Press, New York.Google Scholar
  32. Möller, G. R., Ferry, L., and Snyderman, R., 1978, The inflammatory response and resistance to endotoxin in mice,J. Immunol. 120:116.Google Scholar
  33. Morrison, D. C., and Ryan, J. L., 1979, Bacterial endotoxins and host immune responses, Adv. Immunol. 28:293.PubMedCrossRefGoogle Scholar
  34. Nowakowski, M., Edelson, P. J., and Bianco, G., 1980, Activation of G3H/HeJ macrophages by endotoxin,J. Immunol. 125:2189.PubMedGoogle Scholar
  35. Nowotny, A., 1969, Molecular aspects of endotoxic reactions, Bactenol. Rev. 33:72.Google Scholar
  36. Nowotny, A., Behling, U. H., and Chang, H. L., 1975, Relation of structure to function in bacterial endotoxins. VIII. Biological activities in a polysaccharide-rich fraction,J. Immunol. 115:199.PubMedGoogle Scholar
  37. O’Brien, A., Rosenstreich, D. L., Scher, I., Campbell, G. H., MacDermott, R. P., and Formal, S. B., 1980, Genetic control of susceptibility to Salmonella typhimurium in mice: Role of the LPS gene,J. Immunol. 124:20.PubMedGoogle Scholar
  38. Parant, M., 1979, Biological properties of a new synthetic adjuvant, muramyl dipeptide, Semin. Immunopathol. 2:101.Google Scholar
  39. Parant, M., and Sacquet, E., 1966, Augmentation de la résistance à l’infection du souriceau conventionnel ou axénique après une injection d’endotoxine, C. R. Acad. Sci. Ser. D 262:1914.Google Scholar
  40. Parant, M., Parant, F., Chedid, L., and Boyer, F., 1967, On the nature of some nonspecific host responses in endotoxin-induced resistance to infection, in: The Reticuloendothelial System and Atherosclerosis (N. R. DiLuzio and R. Paoletti, eds.), pp. 275–284, Plenum Press, New York.Google Scholar
  41. Parant, M., Galelli, A., Parant, F., and Chedid, L., 1976, Role of B-lymphocytes in nonspecific resistance to Klebsiella pneumoniae infection of endotoxin-treated mice,J. Infect. Dis. 134:531.PubMedCrossRefGoogle Scholar
  42. Parant, M., Parant, F., and Chedid, L., 1977, Inheritance of lipopolysaccharide-enhanced nonspecific resistance to infection and of susceptibility to endotoxic shock in lipo-polysaccharide low-responder mice, Infect. Immun. 16:432.PubMedGoogle Scholar
  43. Parant, M., Parant, F., and Chedid, L., 1978, Enhancement of the neonate’s nonspecific immunity to Klebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant, Proc. Natl. Acad. Sci. USA 75:3395.PubMedCrossRefGoogle Scholar
  44. Parant, M. A., Parant, F. J., and Chedid, L. A., 1980, Enhancement of resistance to infections by endotoxin-induced serum factor from Mycobacterium bovis BCG-infected mice, Inject. Immun. 28:654.Google Scholar
  45. Peavy, D. L., Baughn, R. E., and Muscher, D. M., 1979, Effects of BCG infection on the susceptibility of mouse macrophages to endotoxin, Infect. Immun. 24:59.PubMedGoogle Scholar
  46. Pistole, T. G., 1975, Biological activity of phthalated endotoxin, Can. J. Microbiol. 21:1291.PubMedCrossRefGoogle Scholar
  47. Rosenstreich, D. L., and Vogel, S. N., 1980, Central role of macrophages in the host response to endotoxin, in: Microbiology 1980 (D. Schlessinger, ed.), pp. 11–15, American Society for Microbiology, Washington, D.C.Google Scholar
  48. Rosenstreich, D. L., Glode, L. M., and Mergenhagen, S. E., 1977, Action of endotoxin on lymphoid cells,J. Infect. Dis. 136(Suppl.):239.CrossRefGoogle Scholar
  49. Rowley, D., 1956, Rapidly induced changes in the level of nonspecific immunity in laboratory animals, Br. J. Exp. Pathol. 37:223.PubMedGoogle Scholar
  50. Ruco, L. P., and Meltzer, M. S., 1978, Defective tumoricidal capacity of macrophages from C3H/HeJ mice,J. Immunol. 120:329.PubMedGoogle Scholar
  51. Rudbach, J. A., Akiya, F. I., Elin, R. J., Hochstein, H. D., Luoma, M. K., Milner, E. C. B., Milner, K. C., and Thomas, K. R., 1976, Preparation and properties of a national reference endotoxin,J. Clin. Microbiol. 3:21.PubMedGoogle Scholar
  52. Russo, M., and Lutton, J. D., 1977, Decreased in vivo and in vitro colony stimulating activity responses to bacterial lipopolysaccharide in C3H/HeJ mice,J. Cell. Physiol. 92:303.PubMedCrossRefGoogle Scholar
  53. Ryan, J. L., Glode, L. M., and Rosenstreich, D. L., 1979, Lack of responsiveness of C3H/HeJ macrophages to lipopolysaccharide: The cellular basis of LPS-stimulated metabolism,J. Immunol. 122:932.PubMedGoogle Scholar
  54. Skidmore, B. J., Chiller, J. M., Morrison, D. C., and Weigle, W. O., 1975, Immunologic properties of bacterial lipopolysaccharide (LPS): Correlation between the mitogenic, adjuvant and immunogenic activities,J. Immunol. 114:770.PubMedGoogle Scholar
  55. Skidmore, B. J., Chiller, J. M., and Weigle, W. O., 1977, Immunologic properties of bacterial lipopolysaccharide (LPS). IV. Cellular basis of the unresponsiveness of C3H/HeJ mouse spleen cells to LPS-induced mitogenesis,J. Immunol. 118:274.PubMedGoogle Scholar
  56. Sultzer, B. M., 1971, Chemical modification of endotoxin, in: Microbial Toxins, Vol. V (S. Kadis, G. Weinbaum, and S.J. Ajl, eds.), pp. 91–126, Academic Press, New York.Google Scholar
  57. Sultzer, B. M., 1972, Genetic control of host responses to endotoxin, Inject. Immun. 5:107.Google Scholar
  58. Sultzer, B. M., and Goodman, G. W., 1977, Characteristics of endotoxin-resistant low-responder mice, in: Microbiology 1977 (D. Schlessinger, ed.), p. 304, American Society for Microbiology, Washington, D.C.Google Scholar
  59. Van Wyck, D. B., Witte, M. H., Witte, C. L., and Strunck, R. C., 1976, Immunologie effects of partial and total splenectomy, in: Immuno-aspects of the Spleen (J. R. Battisto and J. W. Streilein, eds.), pp. 239–248, Elsevier/North-Holland, Amsterdam.Google Scholar
  60. Vas, S. I., Roy, R. S., and Robson, H. G., 1973, Endotoxin sensitivity of inbred mouse strains, Can. J. Microbiol. 19:767.PubMedCrossRefGoogle Scholar
  61. Vogel, S., Moore, R. N., Sipe, J. D., and Rosenstreich, D. L., 1980, BCG-induced enhancement of endotoxin sensitivity in C3H/HeJ mice. I. In vivo studies,J. Immunol. 124:2004.PubMedGoogle Scholar
  62. Watson, J., and Riblet, R., 1974, Genetic control of responses to bacterial lipopolysaccha-rides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic responses to lipopolysaccharide,J. Exp. Med. 140:1147.PubMedCrossRefGoogle Scholar
  63. Watson, J., Largen, M., and McAdam, K. P. W. J., 1978, Genetic control of endotoxic responses in mice,J. Exp. Med. 147:39.PubMedCrossRefGoogle Scholar
  64. Westphal, O., 1975, Bacterial endotoxins, Int. Arch. Allergy Appl. Immunol. 49:1.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Monique Parant
    • 1
  1. 1.Immunothérapie ExpérimentaleInstitut PasteurParis Cedex 15France

Personalised recommendations