An Elevated Level Of Adiponectin And High Molecular Weight Adiponectin In Maintenance Hemodialysis Patients:Its Effects And Clinical Significance

Objective To investigate the systemic adiponectin levels, isformsand the correlation to anthropometric factors in maintenance hemodialysis(MHD)patients. To analyse the influence of ADPN on cytokine release inmonocytic THP-1cells to examine if ADPN might exert proinflammatoryeffects in uremic serum that were apparently counterintuitive with respectto the favourable effects of this peptide.Methods64patients with MHD and20healthy controls wereinvolved in this study. Plasma concentration of Interleukin-6(IL-6), Interleukin-8(IL-8), Monocyte chemotactic protein-1(MCP-1) and adiponectin were measured by Enzyme-linked immuno absorbent assay (ELISA). The levels of serum tumor necrosis factor-α(TNF-α), leptinwere determined by radioimmunoassay (RIA) method. High sensitivityC-reactive protein (CRP) were analysed by photometric immunoassay.The correlation between ADPN and those factors were evaluated.Immunoblots were performed with the plasma sample and ADPN isoforms were detected from controls and MHD patients which was seperated bySDS-PAGE under non-reducing conditions. Uremic sera mixed with ADPNproduced by goat, ADPN specific antibody and InsolutionTMNF-κBactivation inhibitor were added to the cultrum medium of the monocyticTHP-1cells to see the effect of them on the release of IL-8, MCP-1invitro.Results The levels of systemic adiponectin in MHD patients werefound higher and to be approximately twofold and half higher than incontrols. The concentrations of CRP, IL-6and TNF-α were significantlyhigher in MHD than in controls. Multiple regression analysis showed thatBMI was the independent factor of ADPN and inversely correlated withADPN. The proportion of the high molecular weight (HMW) isoform ofadiponectin was higher in MHD than in controls. The parts of the mediumand low molecular weight isoforms of adiponectin were not different. Thesecretion of IL-8,MCP-1were increased in THP-1cells in the presence ofuremic serum and were uremic serum dose-dependent. The release of IL-8,MCP-1in response to adiponectin produced in the goat were found inducedin the cells while induction of cytokines were higher in the presence ofuremic serum. The increase of IL-8, MCP-1by preincubation ofadiponectin for6hours was abrogated by specific ADPN antibody andinhibitor of the NF-κB pathway.Conclusion①The serum adiponectin is increased and influenced by BMI in MHD.HMW-ADPN is most abundance proportions ofadiponectin in the patients with MHD.②Induction of ADPN to IL-8,MCP-1in monocyte dependents on the activation of NF-κB.Our presentdata raise an alternative explantation that ADPN displays proinflammatoryproperty in the milieu of ESRD.③The milieu of ESRD is aproinflammatory state because of high levels of inflammatory cytokine invivo and induction of IL-8, MCP-1in vitro.