Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase (Statins) Suppress Proliferation and Motility of Human CD4+ T Lymphocytes in Culture.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) along with their blood lipid-lowering effect exhibit anti-inflammatory and immunomodulatory activity. We studied the effects of long-term (72-h or longer) exposure of human T lymphocytes in culture to atorvastatin and rosuvastatin (5-80 nM) on their functional activity. Treatment with statins inhibited PHA/IL-2-induced proliferation of CD4+ T lymphocytes isolated from the peripheral blood of healthy donors. This was accompanied by a decrease in the relative content of cells expressing active caspase-3. Addition of mevalonate or fetal bovine serum simultaneously with statins restored proliferative activity of cells. Culturing of CD4+ T lymphocytes with statins in the presence of IL-2 did not significantly affect the expression of chemokine receptors CCR4, CCR5, CXCR3, and CXCR4. Pretreatment with statins suppressed spontaneous and SDF-1-stimulated migration of CD4+ T lymphocytes, but little changed the content of intracellular phosphorylated protein kinases Akt, p38 and p42/44 (ERK1/2). The cellular effects of "lipophilic" atorvastatin were observed at lower concentrations compared to "hydrophilic" rosuvastatin.