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Meperidine attenuates the secretion but not the transcription of interleukin 1 beta in human mononuclear leukocytes
D O McCarthy1, S Murray, D Galagan
1School of Nursing, University of Wisconsin-Madison, USA.
Background:
The infusion of amphotericin-B (AmB) often produces clinically distressing rigors and chills, which promptly abate with intravenous injection of meperidine, although its mechanism of action is unknown.
Objective:
To examine the effects of meperidine on the transcription or secretion of Interleukin 1 beta (IL-1 beta) in human mononuclear leukocytes (MNL) exposed in vitro to the lipopolysaccharide (LPS) contained in Escherichia coli endotoxin or to AmB.
Methods:
Blood was drawn from eight healthy adult volunteers. The blood was centrifuged, and the layer containing MNL was separated; incubated with various combinations of medium, meperidine, and AmB; then tested for IL-1 content to determine the effect of meperidine on MNL secretion of IL-1 beta. To determine the effect on MNL transcription of IL-1 beta, the RNA was extracted from cells and the IL-1 beta was measured using one of two different methods.
Results:
Incubation of human MNL in the presence of LPS or AmB significantly increased transcription of IL-1 beta mRNA and secretion of IL-1 beta. Addition of meperidine to these cultures significantly reduced LPS-induced, but not AmB-induced, secretion of IL-1 beta in vitro. Meperidine did not alter IL-1 beta mRNA levels in MNL exposed to LPS or AmB.
Conclusions:
These data suggest that meperidine decreases rigors and chills in part by decreasing MNL secretion of IL-1 beta through a posttranscriptional mechanism.
Insights
Meperidine reduces fever and chills associated with amphotericin-B (AmB) by decreasing Interleukin-1 beta (IL-1 beta) secretion from human mononuclear leukocytes (MNL) via a posttranscriptional mechanism.
Area of Science:
- Immunology
- Pharmacology
Background:
- Amphotericin-B (AmB) infusion commonly causes rigors and chills.
- Meperidine administration alleviates these symptoms, but its mechanism is unclear.
Purpose of the Study:
- To investigate meperidine's effect on Interleukin-1 beta (IL-1 beta) transcription and secretion.
- To examine IL-1 beta in human mononuclear leukocytes (MNL) stimulated by lipopolysaccharide (LPS) or AmB.
Main Methods:
- Human MNL were isolated from healthy volunteers.
- Cells were incubated with LPS or AmB, with or without meperidine.
- IL-1 beta mRNA and protein levels were measured.
Main Results:
- LPS and AmB increased IL-1 beta mRNA transcription and secretion.
- Meperidine reduced IL-1 beta secretion induced by LPS, but not AmB.
- Meperidine did not affect IL-1 beta mRNA levels.
Conclusions:
- Meperidine may decrease AmB-induced rigors and chills.
- This effect is likely mediated by reducing MNL secretion of IL-1 beta post-transcriptionally.