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Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-.pdf (493.29 kB)

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

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posted on 2023-06-07, 07:06 authored by M Gadina, R Bertini, Manuela MengozziManuela Mengozzi, M Zandalasini, A Mantovani, Pietro Ghezzi
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Experimental Medicine

ISSN

0022-1007

Publisher

Rockefeller University Press

Issue

6

Volume

173

Page range

1305-1310

Event location

United States

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2020-05-27

First Open Access (FOA) Date

2020-05-27

First Compliant Deposit (FCD) Date

2020-05-27

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