MEPERIDINE ATTENUATES THE SECRETION BUT NOT THE TRANSCRIPTION OF INTERLEUKIN-1-BETA IN HUMAN MONONUCLEAR LEUKOCYTES

Background: The infusion of amphotericin-beta (AmB) often produces cli nically distressing rigors and chills, which promptly abate with intra venous injection of meperidine, although its mechanism of action is un known. Objective: To examine the effects of meperidine on the transcri ption or secretion of Interleukin 1 beta (IL-1 beta) in human mononucl ear 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 com binations 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 an d secretion of IL-1 beta. Addition of meperidine to these cultures sig nificantly 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.