Digoxin and digoxin-like immunoreactive factors (DLIF) modulate the release of pro-inflammatory cytokines.
OBJECTIVE
Cardiac glycosides such as digoxin and their endogenous counterpart digoxin-like immunoreactive factor (DLIF) may possess anti-inflammatory properties.


METHODS
Pro-inflammatory cytokines from human peripheral blood mononuclear cells (PBMC) were measured by ELISA using specific antibodies. Immunocytochemistry was used to localize NF-K: B.


RESULTS
Non-stimulated PBMC constitutively secreted minimum amounts of cytokines. LPS (1 mg/L) stimulation lead to steep increases in TNF-alpha, IL-6 and IL-8 concentrations with peak rises at 8 h. An 8 h delay was observed for IL-10. Increases in IL-10 were sustained for18 h period. Significant inhibition (P > 0.05) of TNF-alpha, IL-6 and IL-8 at non-toxic of digoxin concentration (< 100 nM) and DLIF (10 nM digoxin equivalent (de)) was observed whereas no such effect was seen for IL-10. Inhibition of the degradation of activated NF-K: B in the PBMC was observed with the indicated concentrations of digoxin, DLIF or Pyrrolidine dithiocarbamate (PDTC).


CONCLUSIONS
Digoxin and DLIF inhibit the release of proinflammatory cytokines from PBMC via NF-K: B-dependent pathway suggesting an anti-inflammatory effect.
Ihenetu
K
K
Department of Life Sciences/Division of Biomedical and Molecular Science, Texas A&M University-Corpus Christi, 6300 Ocean Dr., Unit 5802, 78412, Corpus Christi, Texas, USA. Kenneth.ihenetu@tamucc.edu
Espinosa
R
R
de Leon
R
R
Planas
G
G
Perez-Pinero
A
A
Waldbeser
L
L
D002298:Cardenolides / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004077:Digoxin / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D002298:Cardenolides; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C498143:RELA protein, human; D012503:Saponins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C034504:digoxin-like factors; D016753:Interleukin-10; D004077:Digoxin