Lethal endotoxic shock

Delgado M, Gomaiiz RP, Martinez C, Abad C, Leceta J (2000) Anti-inflammatory properties of the type 1 and type 2 vasoactive intestinal peptide receptors Role in lethal endotoxic shock. Eur J Immunol 30 3236-3246. 

ASMase-deficient mice are protected in models of lethal endotoxic shock induced by LPS alone (Haimovitz-Friedman et ah, 1997) or LPS after galacto-samine pre-treatment (Garcia-Ruiz et ah, 2003). Also, treatment of mice with the ASMase inhibitor NB6 enhances survival in endotoxemia (Claus et ah,... 

The involvement of arachidonic acid metabolites in endotoxic and septic shock is further supported by studies with essential fatty acid-deficient (EFAD) rats Rats raised on a diet deficient in arachidonic acid become depleted of this substrate necessary for eicosanoid formation. Studies have shown that EFAD rats are significantly more resistant to lethal endotoxic shock than normal rats and do not exhibit plasma elevations in iTxB2 in response to endotoxin This impaired iTxB2 synthesis may be attributed to a depletion of arachidonic acid from phospholipid pools or an increase in (co —9)-eicosatrienoic acid. The latter increases in EFA deficiency and has been reported to inhibit fatty acid cyclo-oxygenase. This possibility is, however, unlikely. Ethyl arachidonic acid supplementation restored the ability of EFAD rats to synthesize iTxB2 in response to endotoxin ". These deficient rats... 

The role of TNF a in vivo is not well understood. It is believed that TNF is required for protection against bacterial, fungal, parasitic, and perhaps even viral infections and other stressful stimuli (562). TNF knockout mice are shown to develop normally. These mice have normal thymus, but their spleen architecture is abnormal and their ability to fight infection is reduced (563). They are also protected from lethal doses of LPS. Knockout studies of the TNF receptor (p60) have shown that mice deficient in this gene are resistant to endotoxic shock but show increased susceptibility to Listeria monocytogenes (564,565). 

The proinflammatory actions of PAF and its elaboration by endothelial cells, leukocytes, and mast cells under inflammatory conditions are well characterized. PAF and PAF-like molecules are thought to contribute to the pathophysiology of inflammatory disorders, including anaphylaxis, bronchial asthma, endotoxic shock, and skin diseases. The plasma concentration of PAF is increased in experimental anaphylactic shock, and the administration of PAF reproduces many of its signs and symptoms, suggesting a role for the autacoid in anaphylactic shock. In addition, mice over expressing the PAF receptor exhibit bronchial hyperreactivity and increased lethality when... 

Toth, P.D., Hamburger, S.A., Hastings, G.H. and Judy, W.V. (1985). Benoxaprofen attenuation of lethal canine endotoxic shock. Circ. Shock, 15, 89-103... 

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