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Immune modulatory effects of statins
Author(s) -
Zeiser Robert
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12902
Subject(s) - mevalonate pathway , immune system , immunology , rhoa , inflammation , biology , rheumatoid arthritis , medicine , pharmacology , signal transduction , reductase , microbiology and biotechnology , enzyme , biochemistry
Summary Despite 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 GTP ases like RhoA, Rac and Ras to the cell membrane. Therefore, l ‐mevalonate 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.