Simvastatin induces interleukin-18 production in human peripheral blood mononuclear cells

Hideo Kohka Takahashi, Shuji Mori, Hiromi Iwagaki, Tadashi Yoshino, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


The effects of statins on immune response depend on the inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and leukocyte function-associated antigen (LFA)-1, which is a ligand of intercellular adhesion molecule (ICAM)-1. Simvastatin, an HMG-CoA reductase inhibitor with mild inhibition of LFA-1, induced the production of interleukin (IL)-18, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in human peripheral blood mononuclear cells (PBMC). The IL-18 production is located upstream of the cytokine cascade activated by simvastatin. Moreover, simvastatin concentration-dependently inhibited the expression of ICAM-1 and induced the expression of CD40 on monocytes. In the presence of IL-18, simvastatin suppressed the expression of ICAM-1 and CD40 as well as the production of IL-12, TNF-α and IFN-γ in PBMC, contributing to the anti-inflammatory effect of simvastatin. The effects of simvastatin were abolished by the addition of the product of the HMG-CoA reductase, mevalonate, indicating the involvement of HMG-CoA reductase in the action of simvastatin.

Original languageEnglish
Pages (from-to)211-216
Number of pages6
JournalClinical Immunology
Issue number3
Publication statusPublished - Sept 2005


  • 3-Hydroxy-3-methylglutaryl coenzyme-A
  • Human
  • Leukocyte function-associated antigen
  • Peripheral blood mononuclear cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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