Abstract 106: Corticosteroid Treatment Induces Structural and Functional Changes in High-Density Lipoproteins

Abstract

Rationale: We have previously shown that high-density lipoproteins (HDL) have potent anti-inflammatory properties. HDL levels are decreased in most inflammatory diseases. Corticosteroid therapy modifies lipoproteins profiles in subjects with chronic obstructive pulmonary disease (COPD) but results from these studies are inconsistent. Here, we hypothesize that in COPD subjects, prednisone treatment induces beneficial structural and functional changes in HDL thus improving HDL anti-inflammatory properties. Objectives: To elucidate the effect of prednisone on (i) HDL size, composition and subpopulation distribution (ii) the lipid and lipoprotein profiles of subjects with COPD and (iii) HDL anti-inflammatory properties. Methods: We recruited COPD subjects (n=11) treated with prednisone and people treated with antibiotics (n=6) for lower respiratory tract infections (control). Blood samples were collected on days 1, 5 of prednisone treatment and 6 weeks post-treatment. The treatment started with a high-dose (>50 mg) and was reduced over a 5-7 day treatment period. We used gel-filtration chromatography to analyse plasma lipoprotein profiles. ApoA-I, apoA-II, apoB levels were determined immunoturbidometrically; total cholesterol, HDL-C, triglyceride and phospholipid concentrations were determined colorimetrically; and size distribution and surface charge of HDL were determined by 2-D gel electrophoresis. HDL was isolated from plasma and incubated for 16h on human endothelial cells (final protein concentration 1 mg/ml). Cells were further stimulated for 5h with TNF-α (0.2 ng/ml). Adhesion molecule expression (ICAM-1 and VCAM-1) was assessed by flow cytometry. Results: Plasma from prednisone treated subjects showed increased apoA-I (36%), apo-B (51%), total cholesterol (13%) and phospholipid (37%) levels and decreased plasma triglycerides (41%) relative to 6 weeks post-treatment. HDL-C levels were higher in subjects that received high-dose prednisone (0.94±0.21 mmol/L) compared to 6 weeks post-treatment (0.65±0.06 mmol/L) and antibiotic-treated subjects (0.43±0.17 mmol/L). HDL diameter in prednisone treated subjects increased from 7.9 nm to 10 nm. HDL from prednisone-treated subjects suppressed ICAM-1 (70%) and VCAM-1 (65%) protein expression more effectively than the HDL from 6-weeks post-treatment (25% and 12% respectively) or the HDL from the antibiotics-treated subjects (36% and 24% respectively) (p<0.05 for all). Conclusions: In this study, we have shown the evidence that high-dose, short-term prednisone treatment increases HDL levels and improves their anti-inflammatory properties.