Calcium channel blockers differentially modulate cytokine production by peripheral blood mononuclear cells

Abstract

Background: Calcium channel blockers (CCB) are known to modulate immune reactions, so the present study was performed to examine the effects of various CCBs that have shown different effects on transcription factors and on the production of pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMC). Methods and Results: PBMC from healthy volunteers were isolated by Ficoll-paque density centrifugation. To study the effect of CCBs, the PBMC were stimulated with lipopolysaccharide or concanavalin A. After 24 h of incubation, the supernatants were harvested and the interleukin (IL)-1α, -1β, and -6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ levels were determined by specific enzyme-linked immunosorbent assay. The production of IL-1α and -1β stimulated with lipopolysaccharide was significantly increased in the presence of amlodipine. In contrast, nifedipine and verapamil suppressed the production of IL-1β, TNF-α, and IFN-γ. Amlodipine and diltiazem significantly increased production of IL-1α stimulated with concanavalin A. Nifedipine inhibited production of IL-1α, IL-6, and IFN-γ. Verapamil suppressed production of IFN-γ. Conclusions: Differential modulation of cytokine production was seen with various CCBs, and the suppressive effect of nifedipine was most prominent.