Apheresis-inducible cytokine pattern change in severe, genetic dyslipidemias

Abstract

Objective: The effects of direct adsorption of lipids LDL-apheresis (DALILDL-a) on plasma cytokines in two Homozygous and heterozygous familial hypercholesterolemic (HozFH, HtzFH) and in four HyperLp(a)lipoproteinemic [HyperLp(a)] patients, were evaluated.

Methods: Plasma, macrophage inflammatory proteins 1α (MIP-1α), macrophage inflammatory proteins 1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted), granulocyte-colony stimulating factor (GCSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-1α (IL-1α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ), concentrations, were measured before and after LDL-a on three consecutive sessions for each patient.

Results: MIP-1α was significantly reduced (P=0.05), while MIP-1β was significantly increased (P=0.05). Plasma MCP-1 was reduced, although not significantly, while RANTES was significantly increased (P=0.05). GCSF and GM-CSF were both significantly reduced (GM-CSF: P=0.05, GCSF: P=0.05, respectively). IL-1α level was significantly reduced (P=0.001). IL-1β, IL-6, and IFN-γ levels were significantly reduced in plasma after apheresis (IL-1β: P=0.001, IL-6: T1 P=0.001; T2 P=0.05, respectively, IFN-γ: P=0.001). IL-2 level in plasma was significantly reduced at T0, and T2, (P=0.001). However, IL-2 level showed a statistically significant increase at T1 (P=0.001). A significant correlation between IL-1α and IFN-γ was found: r=0.882 (P=0.001).

Conclusions: In this study LDL-a induced profound changes in several circulating cytokines and promoted anti-inflammatory and anti-atherogenic cytokine profile in plasma of patients with severe dyslipidemia, with pre-existing angiographically demonstrated Coronary heart disease (CHD), and aortic valvular disease (#=1) (AVD).