Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock

Gadina, M, Bertini, R, Mengozzi, M, Zandalasini, M, Mantovani, A and Ghezzi, P (1991) Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock. Journal of Experimental Medicine, 173 (6). pp. 1305-1310. ISSN 0022-1007

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Abstract

The present study was designed to define the potential ofchlorpromazine (CPZ) as a protective agent against lipopolysaccharide (LPS) toxicity in comparison with glucocorticoids, and to obtain initial correlations with its effects on the levels of tumor necrosis factor (TNF), a pivotal mediator of endotoxic shock. It was found that CPZ protects mice, normal or adrenalectomized, and guinea pigs against lethality of LPS, and inhibited TNF serum levels, like dexamethasone (DEX), a well-known inhibitor ofTNF synthesis. CPZ protected against LPS lethality when administered 30 minutes (min) before, simultaneously, or up to 10 min after LPS and was ineffective when given 30 min after LPS, paralleling the inhibitory effect on TNF production. In another experimental model, where mice were sensitized to LPS toxicity by actinomycin D, CPZ significantly inhibited LPS lethality and hepatotoxicity, whereas under these conditions DEX was inactive. These experiments indicate that CPZ has a protective action in both glucocorticoid-sensitive and -resistant models of endotoxic shock.

Item Type: Article
Keywords: Adrenalectomy, Animals, Chlorpromazine, Dexamethasone, Dose-Response Relationship, Drug, Endotoxins, Guinea Pigs, Lipopolysaccharides, Male, Mice, Shock, Septic, Time Factors, Tumor Necrosis Factor-alpha
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 27 May 2020 09:18
Last Modified: 27 May 2020 09:30
URI: http://sro.sussex.ac.uk/id/eprint/91392

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