Experimental evidence for a significant impairment of host defense for gram-negative organisms by a specific cutaneous toxin produced by severe burn injuries.
Dry heat forms a specific burn toxin in mouse and human skin from a naturally occurring precursor by a polymerization process and not by producing breakdown products. Precursor and toxin are both macromolecular lipid-protein complexes with similar chemical composition and physical structure both occurring in mouse and human skin as well as in serum of burned patients. Specific toxicity resides only in the apoprotein of the polymeric toxic form which also has new specific artificially produced antigenic site or sites. This phenomenon makes it possible to jump the species from man to mouse, shown by the success of specific immunotherapy. Neutral apolar lipids of the coat are contributing in an unspecific but significant manner to the toxic effect. Bacteria are not involved in toxin production nor in toxin activity. The target systems of the toxin are the cell wall membranes of all parenchymal cells of paractically all organs. The toxin apparently causes severe damage of the membrane verified by an increased permeability for compounds which otherwise do not penetrate. This basic cell damage itself is able to kill the animal, depending on the ratio of intact to damaged cells. Sublethal doses of toxin, however, prepare the background upon which bacteremia in burn injuries leads to a lethal sepsis. Finally, the direct toxic action as well as the enhancement of the susceptibility for gram-negative organisms both leading to the lethal outcome can be counteracted by specific passive antitoxic immunotherapy.
D000818:Animals; D000992:Antitoxins / Q000627:therapeutic use; D002056:Burns / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D002250:Carbon Radioisotopes; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D051379:Mice; D011552:Pseudomonas Infections / Q000276:immunology / Q000517:prevention & control*; D011817:Rabbits; D012867:Skin / Q000032:analysis; D014118:Toxins, Biological / Q000302:isolation & purification; D014946:Wound Infection / Q000276:immunology*
D000992:Antitoxins; D002250:Carbon Radioisotopes; D007074:Immunoglobulin G; D014118:Toxins, Biological