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The Active Principle of Bacterial Lipopolysaccharides (Endotoxins) for Cytokine Induction

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Pathophysiology of Shock, Sepsis, and Organ Failure

Abstract

Toxic agents in bacterial cultures have been discov ered in the last decades of the nineteenth century. Pfeiffer described endotoxic in addition to exotoxic activities (Pfeiffer 1892), which include fever (Centanni 1942) and other deleterious effects. Between 1930 and 1940 the first efforts to isolate and enrich biologically active fragments of gram-negative bacteria were successful (Boivin and Mesrobeaunu 1935; Morgan 1937; Goebel et al. 1945) and by the work of Lüderitz and Westphal the endotoxically active material was determined to be a lipopolysaccharide (LPS) (Hartwell and Shear 1943). With the development of the hot phenol/water method (Westphal et al. 1952) the purification of LPS was improved, yielding purified LPS free of nuclei acid and protein. Subsequently, the lipid portion of the LPS molecule was proposed to be responsible for its endotoxic properties, and the term “lipid A” was introduced (Westphal and Lüderitz 1954). In the following three decades, this hypothesis was proven to be correct by the isolation of purified free lipid A, its structural elucidation, and finally the com plete chemical synthesis of lipid A. Detailed com parative investigations of natural and synthetic lip id A showed (1) that the chemical structure as de termined by analytical chemistry was correct and (2) that the biological activity of both natural and synthetic compounds was identical in various in vitro and in vivo biological test systems. At the same time, the successful chemical synthesis (Kusumoto et al. 1990) of lipid A partial structures and analogues allowed us to start investigations on structure-function relationships with regard to en dotoxic and beneficial effects of LPS.

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  1. Research Institute Borstel, Institute for Experimental Biology and Medicine, Parkallee 22, D-2061, Borstel, Germany

    H. Loppnow, H.-D. Flad, E. T. Rietschel & H. Brade

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  1. Ludwig-Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstraße 13, A-1200, Vienna, Austria

    Günther Schlag M. D.  & Heinz Redl Ph. D.  & 

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Loppnow, H., Flad, HD., Rietschel, E.T., Brade, H. (1993). The Active Principle of Bacterial Lipopolysaccharides (Endotoxins) for Cytokine Induction. In: Schlag, G., Redl, H. (eds) Pathophysiology of Shock, Sepsis, and Organ Failure. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76736-4_30

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