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


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)-1alpha, -1beta, and -6, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma levels were determined by specific enzyme-linked immunosorbent assay. The production of IL-1alpha and -1beta stimulated with lipopolysaccharide was significantly increased in the presence of amlodipine. In contrast, nifedipine and verapamil suppressed the production of IL-1beta, TNF-alpha, and IFN-gamma. Amlodipine and diltiazem significantly increased production of IL-1alpha stimulated with concanavalin A. Nifedipine inhibited production of IL-1alpha, IL-6, and IFN-gamma. Verapamil suppressed production of IFN-gamma.


CONCLUSIONS
Differential modulation of cytokine production was seen with various CCBs, and the suppressive effect of nifedipine was most prominent.
Matsumori
Akira
A
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan. amat@kuhp.kyoto-u.ac.jp
Nishio
Ryosuke
R
Nose
Yoshisuke
Y
D017311:Amlodipine / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016207:Cytokines; C508600:IL6 protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C082161:lipopolysaccharide A; D017311:Amlodipine; D007371:Interferon-gamma; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine