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

Abstract

5 The CHI Consortium is detailed in the supplemental material. BACKGROUND. HMG-CoA 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 × 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 FDR of 0.05. Among changes noted were a concordant increase in proinflammatory cytokines (IFN-γ, IL-1β, IL-5, IL-6, and TNF-α) 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. TRIAL REGISTRATION. ClinicalTrials.gov NCT01200836.

The Binary Model of Chronic Diseases Applied to COVID-19

“…Fluvastatin-pretreated donor cells attenuated CTL function in acute graft-versus-host disease mouse model (37). Rosuvastatin suppressed CTL activity in some subpopulations of healthy subjects (38) and HIV-infected patients (39). Direct antiviral effect-inhibition or slowing down viral replication is common to several statins, due to their ability of inhibiting cholesterol production, reducing the availability of some isoprenoids that are essential for regulating the virus life cycle and by inhibiting the activity of regulatory proteins related to virus intracellular life cycle (40).…”

Lipid homeostasis and mevalonate pathway in COVID-19: Basic concepts and potential therapeutic targets

“…Over the last few years, several pharmacological inhibitors, such as statins and nitrogen-containing BPs have been utilized to control cholesterol metabolism in immune cells. A recent prospective study reported a pro-inflammatory role of rouvastatin in subjects with normal levels of cholesterol [ 91 ], despite the large body of evidence that ascribes anti-inflammatory and immunomodulatory properties to statins, suggesting their key role in the treatment of viral infections [ 92 , 93 ]. Among the immunomodulatory roles of statins, it has firstly recognized their ability to repress the major histocompatibility complex (MHC)-II expression on several cell types, such as macrophages, B and activated T lymphocytes [ 94 ].…”

Cholesterol metabolism: a new molecular switch to control inflammation

“…Of special interest will be to address the role of systemic cholesterol in determining the fate of the immune response. In this regard, an interesting study has demonstrated that in healthy individuals, statin treatment increased the levels of pro-inflammatory cytokines in serum, although no functional studies in immune cells were performed [174].…”