Endotoxin lethal effects

B23. Beutler, B., Milsark, I. W., and Cerami, A., Passive immunization against cachectin/tumor necrosis factor protects mice from the lethal effects of endotoxin. Science 229,869-871 (1985)... 

Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc. Natl. Acad. Sci. USA, 76, 5939-59 13 Inage, M., Chaki, H., Kusumoto, S., and Shiba, T. (1980). Synthesis of Lipopolysaccharide corresponding to fundamental structure of Salmonella-type lipid A. Tetrahedron Lett. 21, 3889-3892 Jans son, P.-E., Lindberg, A. A., Lindberg, B., and Wollin, R. (1981). 

Develop normally and are healthy. No difference in their reaction to endotoxin shock, however resist the lethal effects of shock induced by platelet-activating factor. Inflammation induced by arachidonic acid is markedly reduced (Chen et al. 1994 Argentieri et al. 1994). 

Whether or not Hb accentuates lethal effects of endotoxin is also not resolved. When inoculation with living E. coli or endotoxin has been used to induce sepsis in mice, some Hb preparations have been found to demonstrate deleterious effects. " In contrast, other studies using better characterized, modified Hb solutions have failed to confirm these findings, both in mice and in other animal models. ... 

Although endotoxin interacts with many cells throughout the body, and probably does intercalate into membranes in a fairly nonspecific fashion, the lethal effect of LPS seems to be conferred by cells of hematopoietic origin. This fact was revealed by adoptive transfer studies in which crosstransplantation of C3H/HeJ and C3H/HeN hematopoietic stem cells was carried out after lethal irradiation (26). The phenotype of the donor determined the phenotype of the radiation chimera. In separate experiments, it was shown that macrophages were of principal importance in LPS toxicity (27,28). As hematopoietic derivatives, macrophages therefore seem to be the most important responder cells, ultimately conferring the lethal effect of LPS. 

Beutler B, Milsark IW, Cerami A. 1985. Passive immunization against cachectin/ tumor necrosis factor (TNF) protects mice from the lethal effect of endotoxin. Science 229 869-71... 

Galanos C, Freudenberg MA, Reutter W (1979) Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci USA 76 5939-5943... 

The evidence incriminating TNF in the pathogenesis of septic shock is now considerable. However, other cytokines may be involved, perhaps in amplifying TNF production or responses. TNF induces IL-1 synthesis in macrophages and endothelial cells and IL-1 administration enhances the lethal effects of recombinant TNF (W2). More recently it has been shown that the administration of recombinant human IL-1 receptor antagonist IL-lra improves survival in lethal endotoxemia in mice (A12). Indeed the administration of endotoxin alone induces inhibitors of both TNF and IL-1 in human plasma (S48). These findings yet again underline the complexity of the network of cytokines and their inhibition. 

Anthrax, caused by Bacillus anthraciSy is a sporeforming, gram-positive rod that produces a lethal endotoxin. An effective vaccine was discovered by Pasteur in 1881. In the U.S., almost all human infections are cutaneous and limited to workers handling imported goat hair, wool, and hides from endemic regions with poor infectious disease controls. 

Isoflavonoid has been used as dietary biomarkers [103,104], It has been further established that isoflavonoids influence receptor expression [105] and induce immune changes [106,107], The individual variation in metabolism of isoflavones has also been extansively studied [108,109], It has been further demonstrated that flavonoids show antiinflammatory effects on adjuvant arthritis [110], and protect mice from two types of lethal shock caused by endotoxin [111],... 

Quil-A saponin toxicity. Mice fed Quil-A-supplemented diet (a saponin that emulsifies fats and potentiates the immune responses) showed higher level of docosa-pentaenoic acid in the liver. These changes were associated with a significant reduction in the plasma PGEl and PGE2 and thrombohane-B2 levels in response to an intraperitoneal injection of a lethal dose of lipopolysaccharide endotoxin, LDjf, 20 mg/ kg. The data suggest that sesame seed oil and Quil A, when present in the diet, exerted cumulative effects that resulted in a decrease in the levels of dienoic eicosanoids with a reduction in lL-1 P and a con-commitant elevation in the levels of lL-10 that were associated with a marked increase survival in mice . ... 

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