amphotericin-B, meperidine, interleukin-1, endotoxin, mononuclear leukocytes



  1. McCarthy, Donna O.
  2. Murray, Susan
  3. Galagan, Dawn
  4. Gern, James E.
  5. Hutson, Paul R.


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 inEscherichia 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.