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

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.