Release of interleukin-6 and its soluble receptors by activated peripheral blood monocytes is elevated in hypocholesterolemic hemodialysis patients.
BACKGROUND
A reverse association between cholesterol level and cardiovascular disease mortality is observed in hemodialysis (HD) patients; this paradoxical relationship may be explained by the coexistence of inflammation. Interleukin-6 (IL-6) is a central regulator of inflammation; its action is augmented by the soluble IL-6 receptor (sIL-6R) and inhibited by the soluble gp130 (sgp130). In order to investigate the potential association of inflammation with cholesterol levels in the HD population, release of soluble IL-6 components by peripheral blood mononuclear cells (PBMCs) was measured in two groups of HD patients with distinctly different lipid profile and in a control group.


METHODS
Twenty-two HD patients with low serum cholesterol (range 85-171 mg/dl), 23 HD patients with high cholesterol (189-342 mg/dl) and 21 normolipidemic non-renal failure subjects were enrolled in the study. IL-6, sIL-6R and sgp130 were measured by ELISA in the serum and in the supernatant collected from cell cultures of activated or resting PBMCs isolated from all three groups.


RESULTS
Serum IL-6 and sgp130 level was higher while sIL-6R was lower in both groups of HD patients compared to the control group. The ex-vivo release of the IL-6 and sgp130 by unstimulated PBMCs did not differ significantly between the three groups but that of the sIL-6R was higher in non-renal failure than in hypercholesterolemic HD subjects. Production of sIL-6R by stimulated PBMCs was higher in low-cholesterol HD patients (p < 0.001) and the same was valid for the sgp130 release (p = 0.034). Release of IL-6 by activated PBMCs was higher in the low-cholesterol compared to the high-cholesterol HD patients group (p = 0.011 for post hoc test). Major serum lipid fractions were inversely correlated to IL-6 and sIL-6R production from stimulated PBMCs in HD but not in non-renal failure subjects. Finally, release of the sgp130 by PBMCs was significantly reduced in 13 hypertriglyceridemic--and hypercholesterolemic--HD patients.


CONCLUSIONS
Production of soluble components of a crucial pro-inflammatory and potentially atherogenic cytokine, namely the IL-6, by stimulated PBMCs appears to be inversely correlated with the serum cholesterol levels in HD patients.
Tsirpanlis
George
G
Department of Nephrology, General Hospital of Athens, Kriezi 61, Polydroso, Marousi, GR-15125 Athens, Greece. tsipg@hellasnet.gr
Chatzipanagiotou
Stylianos
S
Boufidou
Fotini
F
Kordinas
Vasileios
V
Alevyzaki
Fotini
F
Zoga
Margarita
M
Kyritsis
Ilias
I
Ioannou
Dimitris
D
Fatourou
Alexandra
A
Nicolaou
Chrysoula
C
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood / Q000172:deficiency*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000097:blood*; D006435:Renal Dialysis; D012995:Solubility
D006023:Glycoproteins; D015850:Interleukin-6; D008055:Lipids; D008070:Lipopolysaccharides; D019947:Receptors, Interleukin-6; C480482:glycoprotein 130, human; D002784:Cholesterol