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Meperidine attenuates the febrile response to endotoxin and interleukin-1 alpha in rats
D O McCarthy1, J M Daun, P R Hutson
1School of Nursing, University of Wisconsin-Madison.
Abstract:
Intravenous meperidine is commonly used to treat rigors and chills in febrile patients, though its mechanism of action is unknown. Therefore a laboratory model of pyrogen-induced fever was used to evaluate the effects of meperidine on the febrile response of rats injected with bacterial endotoxin or IL-1 alpha. Fever was measured using a computerized biotelemetry system for the continuous monitoring of body temperature. Injection of meperidine blocked the onset of fever in rats injected with endotoxin and attenuated the febrile response in rats injected with IL-1 beta. Furthermore, incubation of human mononuclear leukocytes (MNL) in the presence of meperidine significantly reduced endotoxin-induced secretion of IL-1 beta in vitro. These data suggest that meperidine decreases rigors and chills by decreasing the "set point" for fever, perhaps by reducing MNL secretion of IL-1 beta.
Insights
Meperidine effectively reduces fever and chills in patients by lowering the body's temperature set point. This study shows meperidine reduces interleukin-1 beta (IL-1 beta) secretion, a key fever-inducing substance.
Area of Science:
- Pharmacology
- Immunology
- Physiology
Background:
- Intravenous meperidine is frequently used to manage rigors and chills in febrile individuals.
- The precise mechanism by which meperidine exerts its antipyretic effects remains largely unknown.
- Fever is a complex physiological response often mediated by pyrogens and cytokines like IL-1 beta.
Purpose of the Study:
- To investigate the mechanism of action of meperidine in mitigating fever and chills.
- To evaluate the impact of meperidine on pyrogen-induced fever in a rat model.
- To determine if meperidine affects the production of key inflammatory cytokines.
Main Methods:
- A laboratory model utilizing pyrogen-induced fever in rats was employed.
- Bacterial endotoxin and IL-1 alpha were used to induce fever.
- Continuous body temperature monitoring was performed using computerized biotelemetry.
- In vitro studies assessed IL-1 beta secretion from human mononuclear leukocytes (MNL) incubated with meperidine.
Main Results:
- Meperidine administration blocked fever onset in rats injected with bacterial endotoxin.
- Meperidine attenuated the febrile response in rats injected with IL-1 beta.
- In vitro, meperidine significantly reduced endotoxin-induced IL-1 beta secretion by MNL.
Conclusions:
- Meperidine appears to decrease rigors and chills by lowering the fever "set point".
- This effect may be mediated by the reduction of IL-1 beta secretion from mononuclear leukocytes.
- Meperidine's mechanism involves modulating the inflammatory cytokine response during fever.