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Calcium antagonists decrease plasma and tissue concentrations of tumor necrosis factor-alpha, interleukin-1 beta, and
R S Hotchkiss1, D F Osborne, G D Lappas
1Department of Anesthesiology, Washington University, St Louis, Missouri 63110, USA.
Shock (Augusta, Ga.)
|May 1, 1995
Summary
Calcium antagonists, like dantrolene, may treat endotoxin-induced inflammation by reducing harmful cytokine levels. These drugs show promise in managing inflammatory disorders mediated by cytokines.
Area of Science:
- Pharmacology
- Immunology
- Toxicology
Background:
- Calcium ions are implicated in endotoxin toxicity and survival rates.
- Calcium's role in regulating cytokine production is under investigation.
- Calcium antagonists may mitigate endotoxin effects by modulating cytokine release.
Purpose of the Study:
- To investigate the protective effects of calcium antagonists against endotoxin challenge in a mouse model.
- To determine if these effects are mediated by reduced cytokine production.
Main Methods:
- Mice were challenged with endotoxin and treated with dantrolene, azumolene, or diltiazem.
- Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and IL-1 beta were measured.
- Cytokine levels in lung, liver, and spleen tissues were also assessed.
Main Results:
- Dantrolene, azumolene, and diltiazem significantly reduced plasma TNF-alpha, IL-1 alpha, and IL-1 beta.
- Dantrolene and azumolene specifically decreased IL-1 alpha and IL-1 beta levels.
- Dantrolene also reduced TNF-alpha and IL-1 alpha in lung, liver, and spleen tissues.
Conclusions:
- Calcium antagonists demonstrate efficacy in reducing endotoxin-induced cytokine storm.
- These findings suggest potential therapeutic applications for calcium antagonists in cytokine-mediated inflammatory conditions.