TY - JOUR TI - Release of interleukin-6 and its soluble receptors by activated peripheral blood monocytes is elevated in hypocholesterolemic hemodialysis patients AU - Tsirpanlis, G AU - Chatzipanagiotou, S AU - Boufidou, F AU - Kordinas, V AU - and Alevyzaki, F AU - Zoga, M AU - Kyritsis, I AU - Ioannou, D and AU - Fatourou, A AU - Nicolaou, C JO - American Journal of Nephrology PY - 2005 VL - 25 TODO - 5 SP - 484-490 PB - Karger SN - 0250-8095, 1421-9670 TODO - 10.1159/000087921 TODO - soluble IL-6 receptor; peripheral blood mononuclear cell; reverse epidemiology; cardiovascular disease; renal failure; triglycerides; cholesterol; inflammation; cell culture; cytokines; soluble receptors; lipids TODO - 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 sgp 130 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. Conclusion: 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. Copyright (C) 2005 S. Karger AG, Basel. ER -