Treatment of Burn Patients with Polymyxin B: Effects on Lymphokine Regulation

  • R. A. Winchurch
  • G-X. Xiao
  • A. M. Munster
  • W. H. Adler
  • C. White
  • B. Bender
Conference paper


Endotoxins are among the most potent agents known to affect mammalian metabolism. The body’s responses to bacterial endotoxins were recognized as early as the 1920s by such notables as Sanarelli [1], Shwartzman [2], and Hanger [3]. In 1924 Sanarelli observed that animals injected with a small, sublethal dose of Vibrio cholerae died when subsequently exposed to a nonlethal dose of colon bacilli. Soon afterward Shwartzman described this phenomenon in detail and characterized the reaction which still bears his name; namely, the ability of substances produced by gram-negative bacteria to induce a temporary, nonspecific sensitivity which results in local or systemic hemorrhagic necrosis upon subsequent challenge. In the 60 odd years since these early reports much has been written about the biological effects of endotoxins. Within this compendium the greatest bulk of the literature concerns the effects of endotoxins on host resistance. This devotion to the study of endotoxins is not at all surprising since all mammalian species carry a large and potentially fatal burden of endotoxins derived from the gram- negative flora of the gut. In the normal, young adult animal this burden does not appear to affect the host adversely provided that the mechanisms for containment and detoxification are intact. When the ability to contain endotoxins is compromised, as might occur in the aged [4], or when detoxification fails as in the case of liver malfunction [5], the systemic exposure to endotoxins can produce dramatic changes in the host defense posture.


Thermal Injury Natural Killer Activity Endotoxin Exposure Burn Patient Young Adult Animal 
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  1. 1.
    Sanarelli G (1924) Experimental cholera. Ann de L’Inst Pasteur 38: 11Google Scholar
  2. 2.
    Shwartzman G (1928) Studies on Bacillus typhosa toxic substances. J Exp Med 48: 247PubMedCrossRefGoogle Scholar
  3. 3.
    Hanger FM (1956) In: Boyd WC (ed) Fundamentals of immunology. Interscience, New York, p 457Google Scholar
  4. 4.
    Winchurch RA, Birmingham W, Hilberg C, Munster A (1982) Effects of endotoxin on immunity in aging mice. Cell Immunol 67: 384PubMedCrossRefGoogle Scholar
  5. 5.
    Trejo RA, Di Luzio NR (1971) Impaired detoxification as a mechanism of lead acetate-induced hypersensitivity to endotoxin. Proc Soc Exp Biol Med 136: 889PubMedGoogle Scholar
  6. 6.
    Cardis DT, Reinhold RB, Woodruff PWH, Fine J (1972) Endotoxaemia in man. Lancet 1: 1381CrossRefGoogle Scholar
  7. 7.
    Cuevas P, Shiyama M, Koizumi S, Woodruff R, Kaufman A, Fine J (1974) Role of endotoxaemia of intestinal origin in early death form large burns. Surg Gynecol Obstet 138: 725PubMedGoogle Scholar
  8. 8.
    Stumacher RJ, Kovnat MJ, McCabe WR (1973) Limitations of the usefulness of the limulus assay for endotoxin. N Engl J Med 288: 1261PubMedCrossRefGoogle Scholar
  9. 9.
    Elin RJ, Robinson RA, Levine AS, Wolff SM (1975) Lack of clinical usefulness of the limulus test in the diagnosis of endotoxemia. N Engl J Med 293: 521PubMedCrossRefGoogle Scholar
  10. 10.
    Thomas LLM, Sturk A, Kahle LH, ten Cate JW (1981) Quantitative endotoxin deter-mination in blood with a chromogenic substrate. Clin Chim Acta 116: 63PubMedCrossRefGoogle Scholar
  11. 11.
    Winchurch RA, Thupari JN, Munster AM (1987) Endotoxin in burn patients: levels of circulating endotoxins are related to burn size. Surgery 102: 808PubMedGoogle Scholar
  12. 12.
    Butler T, Smith E, Hammarstrom L, Moller G (1977) Polymyxins as inhibitors of polyclonal B cell activators in murine lymphocyte cultures. Infect Immun 16: 449PubMedGoogle Scholar
  13. 13.
    Jacobs DM, Morrison DC (1977) Inhibition of the mitogenic response to lipopolysaccharide ( LPS) in mouse spleen cells by polymyxin B. J Immunol 118: 21PubMedGoogle Scholar
  14. 14.
    Chiccone TG, Munster AM, Birmingham W, Winchurch RA (1983) Successful immunomodulation in burned animals and human beings with homeopathic doses of polymyxin B. J Burn Care Rehabil 4: 153CrossRefGoogle Scholar
  15. 15.
    Winchurch RA, Munster AM (1983) The involvement of bacterial lipopolysaccharides in trauma-induced immune depression. In: Ninnemann J (ed) Traumatic injury: infection and other immunologic sequelae. University Park, Baltimore, p 103Google Scholar
  16. 16.
    Munster AM, Winchurch RA, Thupari JN, Ernst CB (1986) Reversal of postburn immunosuppression with low-dose polymyxin B. J Trauma 26: 995PubMedCrossRefGoogle Scholar
  17. 17.
    Bender BS, Winchurch RA, Thupari JN, Proust JJ, Adler WH, Munster AM (1988) Depressed natural killer cell function in thermally injured adults: successful in vivo and in vitro immunomodulation and the role of endotoxin. Clin Exp Immunol 71: 120PubMedGoogle Scholar
  18. 18.
    Antonacci AC, Gupta S, Good RA, Shires GT, Fernandes G (1983) Natural killer and antibody-dependent cytotoxicity following thermal injury in humans. Curr Surg 40: 20PubMedGoogle Scholar
  19. 19.
    Stein MD, Gamble DN, Klimpel KD, Herndon DH, Klimpel GR (1984) Natural killer cell defects resulting from thermal injury. Cell Immunol 86: 551PubMedCrossRefGoogle Scholar
  20. 20.
    Wolfe JHN, Saporoschetz AB, Young AE, O’Connor NE, Mannick JA (1981) Suppressive serum, suppressor lymphocytes and deaths from burns. Ann Surg 193: 513PubMedGoogle Scholar
  21. 21.
    Ozkan AN, Ninnemann JL (1985) Suppression of in vitro lymphocyte and neutrophil responses by a low molecular weight suppressor active peptide from burn-patient sera. J Clin Immunol 5: 172PubMedCrossRefGoogle Scholar
  22. 22.
    Ninnemann JL, Stockland AE (1984) Participation of prostaglandin E in immunosuppression following thermal injury. J Trauma 24: 201PubMedCrossRefGoogle Scholar
  23. 23.
    Teodorczyk-Injeyan JA, Sparkes BG, Mills GB, Falk RE, Peters WJ (1987) Impaired expression of interleukin-2 receptor (I1-2R) in the immunosuppressed burn patient: reversal by exogeneous 11-2. J Trauma 27: 180PubMedCrossRefGoogle Scholar
  24. 24.
    Teodorczyk-Injeyan JA, Sparkes BG, Mills GB, Peters WJ, Falk RE (1986) Impairment of T cell activation in burn patients: a possible mechanism of thermal injury-induced immunosuppression. Clin Exp Immunol 65: 570PubMedGoogle Scholar
  25. 25.
    Roderick ML, Wood JJ, O’Mahony JB, Davis CF, Grbic JT, Demling RH, Mouse MM, Saporoschetz I, Jordan A, D’Eon P, Mannick J A (1986) Mechanisms of immunosuppression associated with severe nonthermal traumatic injuries in man: production of interleukin 1 and 2. J Clin Immunol 6: 310CrossRefGoogle Scholar
  26. 26.
    Roderick ML, Saporoschetz I, Wood J, Davis CF, Mannick JA (1986) Serum suppression of interleukin 2 (11–2) production and IL-2 action in thermal injury. Surg Forum 36: 98Google Scholar

Copyright information

© Springer-Verlag, Berlin Heidelberg 1989

Authors and Affiliations

  • R. A. Winchurch
  • G-X. Xiao
  • A. M. Munster
  • W. H. Adler
  • C. White
  • B. Bender

There are no affiliations available

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