Heart attacks and strokes are predominantly caused by atherosclerosis, a chronic inflammatory condition, where immune cells (monocytes, macrophages, and T-cells) are continuously recruited into the arterial wall where they accumulate cholesterol. The resulting arterial plaques may rupture, triggering blood clot formation and the blockage of blood supply to the heart (heart attack) or brain (stroke).

Statins are lipid-lowering drugs which inhibit cholesterol synthesis, decreasing plasma cholesterol levels, thereby the growth of cholesterol filled inflammatory cells within the arterial wall. Statins appear to possess additional anti-inflammatory properties which may reduce arterial inflammation. This research investigates the anti-inflammatory effects of atorvastatin, to determine how it may alter the levels of inflammatory markers within plaques. This was achieved using the model mixed cell culture system of peripheral blood mononuclear cells (PBMCs), consisting predominately of T-cells and monocytes. PBMCs isolated and prepared from whole human blood were cultured with varying levels of atorvastatin treatment in combinations with the inflammatory activator interferon-γ (IFN-γ). PBMC activation was quantified by measuring the production of inflammatory markers 7,8-dihydroneopterin, neopterin and kynurenine by HPLC.

Experimental results demonstrated that atorvastatin treatment of PBMCs in various combinations including IFN- γ activation, consistently produced an anti-inflammatory effect by inhibiting the production of respective inflammatory markers. In contrast, treatment conditions including IFN-γ only and DMSO produced statistically significant increases in inflammatory marker production. The TNP/NP ratios produced for atorvastatin treatments indicate a greater level of oxidative stress compared to inflammation; however, the mechanism by which this occurs remains unclear. The experimental results provide evidence for atorvastatin inhibiting IFN-γ activated production of 7,8-dihydroneopterin, neopterin and kynurenine in PBMCs. These results suggest atorvastatin may possess anti-inflammatory effects within atherosclerotic plaques.