Immune modulatory effects of statins

Abstract

SummaryDespite major advances in recent years, immunosuppressive regimens for multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and graft-versus-host disease still have major adverse effects and immunomodulation rather than immune paralysis would be desirable. Statins inhibit the rate-limiting enzyme of the L-mevalonate pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. It was shown that blocking the L-mevalonate pathway reduces inflammation through effects on downstream metabolites of the pathway including farnesylpyrophosphates and geranylgeranylpyrophosphates, which are essential for the attachment of GTPases like RhoA, Rac and Ras to the cell membrane. Therefore, Lmevalonate pathway downstream products play critical roles in the different steps of an immune response including immune cell activation, migration, cytokine production, immune metabolism and survival. This review discusses the relevance of the different metabolites for the immunomodulatory effect of statins and connects preclinical results with data from clinical studies that tested statins for the treatment of different inflammatory diseases.

Statin‐dependent modulation of mitochondrial metabolism in cancer cells is independent of cholesterol content

“…Statins that specifically target the HMG-CoA reductase inhibiting de novo Chol synthesis also display pleiotropic effects (36,37). Statins have been reported to alter mitochondrial function in skeletal muscle (38,39), but the information available regarding the effects on mitochondria in cancer cells is scarce (40).…”

Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus

“…However, this is a pleiotropic class of drugs that also exerts several anti-inflammatory effects (43, 544). Despite these anti-inflammatory effects, several studies have now shown statin use to be associated with an increased risk for T2DM (89, 91, 381, 410).…”

Lipid-lowering therapy and renin-angiotensin-aldosterone system inhibitors in the era of the COVID-19 pandemic

“…Therefore, as well as immunomodulation, COVID-19 treatment should also target reduction of inflammation. In this context, statins have been consistently reported to exert immunomodulatory and anti-inflammatory properties [20][21][22][23][24][25][26][27][28][29][30]. Also, it was previously suggested that statins could enhance host defence and suppress inflammation, thus representing a practical and inexpensive adjunctive or alternative host-directed treatment for infections by viruses, fungi, protozoa, and bacteria [31].…”