Action profiles of statins and calcineurin inhibitors during human mixed lymphocyte reaction

Hideo Kohka Takahashi, Hiromi Iwagaki, Takahito Yagi, Toru Kanke, Keyue Liu, Tadashi Yoshino, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The cell-to-cell interaction through binding intercellular adhesion molecule (ICAM)-1 and CD40 on monocytes and their ligands such as lymphocyte function-associated antigen (LFA)-1 and CD40 ligand (CD40L) on T-cells plays roles in cytokine production and T-cell proliferation. Interleukin (IL)-18, which is elevated in the plasma during acute rejection after organ transplantation, induces the expression of ICAM-1 and CD40 on monocytes, the production of interferon (IFN)-γ and IL-12 and the proliferation of T-cells during the human mixed lymphocyte reaction (MLR). In addition to the cholesterol lowering effect, statins improve patient survival and decrease rejection episodes in transplant recipients. In the present study, we investigated the difference of effect of statins and calcineurin inhibitors during MLR. 3-Hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, fluvastatin and pravastatin and statin-derived LFA-1 inhibitors, LFA703 and LFA878, which did not inhibit HMG-CoA reductase, suppressed the production of IFN-γ and IL-12 and the lymphocyte proliferation as well as the expression of ICAM-1 and CD40 on monocytes regardless of the presence of IL-18. However, the calcineurin inhibitors, tacrolimus and cyclosporine A (CsA), inhibited the IL-18-enhanced cytokine production and lymphocyte proliferation without any effect on the adhesion molecule expression. Thus, the action mechanism of stain is different from that of calcineurin inhibitors.

Original languageEnglish
Pages (from-to)324-332
Number of pages9
JournalClinical Immunology
Volume123
Issue number3
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Calcineurin inhibitors
  • IL-18
  • Mixed lymphocyte reaction
  • Statins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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