Oxidative Stress Influences CC-Chemokine Levels in Hemodialyzed Patients

Abstract

Background: Increased oxidative stress (SOX) has been reported in hemodialyzed (HD) patients, but its influence on CC-chemokine levels remains unknown. Methods: The levels of 3 distinct SOX markers (Cu/Zn superoxide dismutase (Cu/Zn SOD), total lipid peroxide, and autoantibodies against oxidized LDL (OxLDL-Ab)), as well as those of 4 CC-chemokines (monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory proteins (MIP-1α, MIP-1β), regulated upon activation, normal T cell expressed and secreted (RANTES), and tumor necrosis factor-α (TNF-α)) were measured pre- and post-HD session in 15 HD patients with cardiovascular disease (CVD) and 12 HD patients without CVD (pre- and post-HD session) and 17 controls. Results: Cu/Zn SOD levels were elevated in HD patients (both before and after HD) compared to controls (p < 0.001). Total lipid peroxide levels were similar in the controls in pre-dialysis samples, but were increased after a HD session (p < 0.001). Pre-dialysis OxLDL-Ab levels were increased only in the HD group with CVD compared to controls (p < 0.05). The pre-dialysis plasma levels of TNF-α (p < 0.001), MCP-1 (p < 0.001) and MIP-1β (p < 0.01) were increased both in all HD patients and subgroups with CVD when compared to the controls, and remained significantly elevated when measured after HD. Dialysis increased MCP-1 (p < 0.05) and MIP-1β (p < 0.001) levels as compared to the controls as well as in patients without CVD. Plasma RANTES was significantly lower before HD (p < 0.05) and after HD (p < 0.001) in patients with CVD. Patients without CVD and all HD patients also had lower RANTES before and after HD when compared to controls (all p < 0.001). A positive correlation was observed between plasma pre-dialysis Cu/Zn SOD levels and the other SOX markers (all p < 0.05), age (p < 0.05) and duration of hemodialysis (p < 0.001). A positive relationship existed between plasma Cu/Zn SOD levels and those of MCP-1, MIP-1β and TNF-α (all p < 0.001). RANTES levels negatively correlated with Cu/Zn SOD (p < 0.0001).TNF-α positively correlated with age (p < 0.05), total lipid peroxide (p = 0.010), MCP-1 (p < 0.01) and MIP-1β levels (p < 0.01). An identifiable association exists between MCP-1 and MIP-1β levels (p < 0.01), whereas both MCP-1 and MIP-1β were inversely correlated with RANTES (both p < 0.05). Conclusion: Our data indicate for the first time a probable functional relationship between oxidative stress and CC-chemokine levels in hemodialyzed patients, particularly in those with cardiovascular disease. This relationship may represent one of the mechanisms involved in the progression of atherosclerosis in these patients.