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Immunology. 2018 May;154(1):69-75. doi: 10.1111/imm.12902. Epub 2018 Feb 20.

Immune modulatory effects of statins.

Author information

1
Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Centre, Freiburg, Germany.

Abstract

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 GTPases 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.

KEYWORDS:

T helper type 2; inflammation; tolerance; transplantation

PMID:
29392731
PMCID:
PMC5904709
[Available on 2019-05-01]
DOI:
10.1111/imm.12902
[Indexed for MEDLINE]

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