Effects of corticosteroid treatment on high-density lipoprotein distribution and function

Abstract

The studies in this thesis investigate the effects of corticosteroid therapy in subjects with COPD on the size, composition, distribution and anti-inflammatory properties of HDL. Subjects with COPD were treated for 1 week with prednisone. Control subjects with lower respiratory tract infection were treated for 2 weeks with antibiotics. Blood was collected on days 1 and 5 after commencing treatment, and at 6 weeks post-treatment. Treatment of COPD subjects with prednisone increased plasma HDL-C and apo A-I levels and decreased triglyceride levels but had no effect on circulating concentrations of apoA-II, apoB, total cholesterol or phospholipids. Prednisone treatment was associated with an increase in the total cholesterol content of HDL and HDL particle size. The change in HDL size in these subjects was associated with an increase in large apoA-I-, apoA-IV- and apoE-containing HDL particles. The observed changes in HDL size and composition were also associated with a concomitant reduction in CETP activity. HDL isolated from COPD subjects after 1 day and 5 days of prednisone treatment inhibited expression of ICAM-1 and VCAM-1 in vivo in cultured HCAECs more effectively than control HDL isolated 6 weeks post-treatment. Treatment with high-dose prednisone decreased circulating levels of the anti-inflammatory proteins, MCP-1, soluble ICAM-1 and soluble VCAM-1 in COPD subjects. The studies provide evidence that high-dose prednisone therapy increases plasma HDL-C and apoA-I levels, and influence HDL sub-population distribution, size and remodelling, possibly by inhibiting CETP. Furthermore, these studies establish that the HDL from prednisone-treated COPD subjects consist of large apoA-I-, apoA-IV- and apoE-containing HDL particles that are known to be anti-inflammatory in vitro, thus raising the possibility that the beneficial effects of corticosteroid treatment in people with COPD may be mediated, at least in part, by the anti-inflammatory properties of HDL.