title: Inhibitory effects of fluvastatin on cytokine and chemokine production by peripheral blood mononuclear cells in patients with allergic asthma.
abstract: BACKGROUND
  Statins have anti-inflammatory effects on immune cells.
  
  
  OBJECTIVE
  To investigate the immunomodulatory effects of fluvastatin on peripheral blood mononuclear cells (PBMCs) after allergen-specific and non-allergen-specific stimulation in patients with asthma and in healthy subjects.
  
  
  METHODS
  PBMCs from seven patients with asthma who showed elevated immunoglobulin (Ig)E to house dust mite were isolated and stimulated with Dermatofagoides farinae, purified protein derivative, and phytohaemagglutinin (PHA) in the presence or absence of fluvastatin. PBMCs from seven healthy subjects were stimulated with PHA. The effects of fluvastatin on cell proliferation and production of cytokines (interferon [IFN]-gamma and interleukin [IL]-5) and chemokines (chemokine CXC motif, ligand [CXCL10], and CC chemokine ligand [CCL17]) were measured. Migration of T helper (Th)1 and Th2 cell lines was also investigated. The expression of CXCR3 and CCR4 was analysed with flow cytometry. Steroid-insensitive PBMCs induced by preculture with IL-2 and IL-4 were also evaluated. Some experiments were performed in the presence of mevalonic acid.
  
  
  RESULTS
  Fluvastatin inhibited the proliferation of PBMCs and decreased the production of IL-5, IFN-gamma, CCL17, and CXCL10 after allergen-specific and non-allergen-specific stimulation; all these effects, except for decreased CXCL10 production, were partially reversed by mevalonic acid. Culture supernatants obtained in the presence of fluvastatin prevented the migration of Th1 and Th2 cell lines in a dose-dependent manner. In addition, CCR4 and CXCR3 expression on CD4(+) T cells was not affected by the presence of fluvastatin. Fluvastatin inhibited the proliferative response of steroid-insensitive PBMCs to phytohaemagglutinin.
  
  
  CONCLUSIONS
  Fluvastatin has inhibitory effects on cytokine and chemokine production, and thus might be used as a potential therapeutic agent in severe asthma.
authors.affiliation: First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: K T R
authors.initials: KT
authors.lastname: Samson
authors.forename: K
authors.initials: K
authors.lastname: Minoguchi
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Oda
authors.forename: T
authors.initials: T
authors.lastname: Yokoe
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Adachi
mesh_terms: D000328:Adult; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D054414:Chemokine CCL17; D054357:Chemokine CXCL10; D018925:Chemokines / Q000276:immunology*; D019742:Chemokines, CC / Q000276:immunology; D019743:Chemokines, CXC / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005229:Fatty Acids, Monounsaturated / Q000276:immunology* / Q000627:therapeutic use; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000276:immunology* / Q000627:therapeutic use; D007211:Indoles / Q000276:immunology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008798:Mevalonic Acid / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; C106230:CCL17 protein, human; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D054414:Chemokine CCL17; D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D015848:Interleukin-5; D010835:Phytohemagglutinins; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D000077340:Fluvastatin; D007371:Interferon-gamma; D008798:Mevalonic Acid