IMMUNE RESPONSE OF CULTURED MONOCYTES OF ATHEROSCLEROTIC PATIENTS RECEIVING STATIN THERAPY

Area of Science:

• Immunology
• Cardiovascular Medicine
• Pharmacology

Background:

• Atherosclerosis is a chronic inflammatory disease characterized by lipid deposition and immune cell infiltration in arterial walls.
• Monocytes/macrophages play a crucial role in the inflammatory processes underlying atherosclerosis.
• Statins are widely used for lipid-lowering but also possess pleiotropic anti-inflammatory effects.

Purpose of the Study:

• To evaluate the impact of hydrophilic (rosuvastatin) and lipophilic (atorvastatin) statins on the inflammatory response of monocytes/macrophages from atherosclerotic patients.
• To assess the effect of statin therapy on the secretion of key inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), by circulating monocytes.
• To investigate the relationship between serum lipid levels and monocyte inflammatory cytokine production in patients with coronary atherosclerosis.

Main Methods:

• Inclusion of three groups: 20 patients receiving atorvastatin, 20 receiving rosuvastatin, and 20 without statin therapy, all with coronary atherosclerosis.
• Isolation of CD14+ monocytes from whole blood via immunomagnetic separation.
• Culture of isolated monocytes for 7 days with or without lipopolysaccharide (LPS) stimulation, followed by ELISA measurement of TNF-α and IL-1β secretion.

Main Results:

• Both atorvastatin and rosuvastatin significantly reduced basal TNF-α secretion compared to the statin-free group.
• Rosuvastatin, but not atorvastatin, significantly reduced basal IL-1β secretion.
• Both statins significantly reduced LPS-stimulated IL-1β secretion, while TNF-α secretion differences were not significant. Rosuvastatin also reduced re-stimulated TNF-α secretion.

Conclusions:

• Statin therapy demonstrably decreases inflammatory cytokine secretion from monocytes in patients with coronary atherosclerosis.
• Rosuvastatin exhibited a more pronounced effect on reducing inflammatory cytokine secretion compared to atorvastatin.
• The observed reduction in TNF-α and IL-1β secretion correlated with lower total cholesterol and LDL serum levels.