The present study was designed to define the potential of chlorpromazine (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 of TNF 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.
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1 June 1991
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June 01 1991
Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock.
M Gadina,
M Gadina
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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R Bertini,
R Bertini
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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M Mengozzi,
M Mengozzi
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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M Zandalasini,
M Zandalasini
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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A Mantovani,
A Mantovani
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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P Ghezzi
P Ghezzi
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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M Gadina
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
R Bertini
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
M Mengozzi
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
M Zandalasini
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
A Mantovani
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
P Ghezzi
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1991) 173 (6): 1305–1310.
Citation
M Gadina, R Bertini, M Mengozzi, M Zandalasini, A Mantovani, P Ghezzi; Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock.. J Exp Med 1 June 1991; 173 (6): 1305–1310. doi: https://doi.org/10.1084/jem.173.6.1305
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