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 lipid-protein complexes with similar chemical composition and physical structure, occurring in mouse and human skin and in serum of burned patients. Specific toxicity resides only in the apoprotein of the polymeric toxic form. Bacteria are not involved in toxin production or in toxin activity. The target systems of the toxin are the cell wall membranes of all parenchymal cells of practically all organs. The toxin apparently causes severe membrane damage 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 prepare the background upon which bacteremia in burn injuries leads to a lethal sepsis. The direct toxic action and the enhancement of the susceptibility for gram-negative bacteria [especially Pseudomonas aeruginosa] can be counteracted by specific passive antitoxic immunotherapy.