Effects of rosuvastatin on the immune system in healthy volunteers with norms serum cholesterol

BACKGROUND. HMG-LOA reductase inhibitors (statins) are prescribed to millions of people. Statins are antiinflammatory independent of their cholesterol-reducing effects. To date, most reports on the immune effects of statins have assayed a narrow array of variables and have focused on cell lines, rodent models, or patient cohorts. We sought to define the effect of rosuvastatin on the immunome of healthy, normocholesterolemic subjects. METHODS. We conducted a prospective study of rosuvastatin (20 mg/d x 28 days) in 18 statin-naive adults with LDL cholesterol <130 mg/dL. A panel of >180 immune/biochemical/endocrinologic variables was measured at baseline and on days 14, 28, and 42 (14 days after drug withdrawal). Drug effect was evaluated using linear mixed-effects models. Potential interactions between drug and baseline high-sensitivity C-reactive protein (hsCRP) were evaluated. RESULTS. A wide array of immune measures changed (nominal P < 0.05) during rosuvastatin treatment, although the changes were modest in magnitude, and few met an FOR of 0.05. Among changes noted were a concordant increase in proinflammatory cytokines (IFN-gamma, IL-1 beta,1L-5,1L-6, and TNF-alpha) and peripheral blood neutrophil frequency, and a decline in activated Treg frequency. Several drug effects were significantly modified by baseline hsCRP, and some did not resolve after drug withdrawal. Among other unexpected rosuvastatin effects were changes in erythrocyte indices, glucose-regulatory hormones, CD8(+) T cells, and haptoglobin. CONCLUSION. Rosuvastatin induces modest changes in immunologic and metabolic measures in normocholesterolemic subjects, with several effects dependent on baseline CRP. Future, larger studies are warranted to validate these changes and their physiological significance.