Meperidine Attenuates the Secretion But Not the Transcription of Interleukin 1β in Human Mononuclear Leukocytes

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 1β (IL-1β) 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-1β. To determine the effect on MNL transcription of IL-1β, the RNA was extracted from cells and the IL-1β 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-1β mRNA and secretion of IL-1β. Addition of meperidine to these cultures significantly reduced LPS-induced, but not AmB-induced, secretion of IL-1β in vitro. Meperidine did not alter IL-1β 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-1β through a posttranscriptional mechanism.