Chlorpromazine protection against interleukin-1 and tumor necrosis factor-mediated activities in vivo.
Interleukin (IL-1) and tumor necrosis factor (TNF) are thought to play a key role in septic shock and inflammation. We had previously shown that chlorpromazine (CPZ) has a protective effect in various models of endotoxic shock and IL-1 toxicity. We have tested the effect of CPZ on several activities of IL-1 in vivo. CPZ (4 mg/kg) inhibited increases in serum corticosterone, triglycerides and serum amyloid A (SAA). Chlorpromazine also antagonized these same effects when they were induced by endotoxin or TNF, suggesting that this activity could be implicated in the protective effect of CPZ in various models of endotoxic shock and IL-1 lethality.
Bertini
R
R
Istituto di Richerche Farmacologiche Mario Negri, Milano, Italy.
Mengozzi
M
M
Bianchi
M
M
Sipe
J D
JD
Ghezzi
P
P
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004435:Eating / Q000187:drug effects; D005340:Fibrinogen / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D008297:Male; D051379:Mice; D015290:Second Messenger Systems / Q000187:drug effects; D000685:Serum Amyloid A Protein / Q000378:metabolism; D012772:Shock, Septic / Q000209:etiology / Q000517:prevention & control; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology
D007375:Interleukin-1; D000685:Serum Amyloid A Protein; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D002746:Chlorpromazine; D003345:Corticosterone