Protective effect of chlorpromazine against the lethality of interleukin 1 in adrenalectomized or actinomycin D-sensitized mice.
Interleukin 1 (IL-1) and Tumor Necrosis Factor (TNF) are thought to play a key role in septic shock and inflammation. We have tested the effect of dexamethasone (DEX) and chlorpromazine (CPZ) on the lethal effect of IL-1, TNF and endotoxin. Two different experimental models were used to sensitize mice to the lethal effect of IL-1: adrenalectomy and pretreatment with actinomycin D. CPZ (4 mg/kg) was found to protect mice against IL-1 and endotoxin toxicity in all cases, while DEX had a protective effect only in adrenalectomized mice. In contrast to its protective effect against IL-1 and endotoxin, CPZ did not protect mice against TNF. These findings might be useful in the analysis of the differences in the actions of IL-1 and TNF in vivo, and in the development of new drugs preventing their toxicity.
Bertini
R
R
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Bianchi
M
M
Mengozzi
M
M
Ghezzi
P
P
D000315:Adrenalectomy; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004926:Escherichia coli; D007375:Interleukin-1 / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003907:Dexamethasone; D002746:Chlorpromazine