title: Simvastatin inhibits cytokines in a dose response in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the effects of simvastatin in peripheral blood mononuclear cell (PBMC) cytokines profiles and correlate with the disease state of rheumatoid arthritis (RA) patients.
  
  
  METHODS
  The PBMC from 22 RA patients were purified and stimulated or not stimulated with phorbol myristate acetate/ionomycin and were treated with simvastatin in different doses. Cytokine levels were quantified by ELISA and patients were assessed for clinical and laboratory variables. This assessment included disease activity measures [Clinical Disease Activity Index (CDAI), Disease Activity Score for 28 joints (DAS28)] and a Health Assessment Questionnaire.
  
  
  RESULTS
  The IL-17A, IL-6, IL-22 and IFN-γ were significantly reduced in a dose response after simvastatin treatment (50 μM, p = 0.0005; p < 0.0001; p < 0.02; p = 0.0005, respectively). The IL-17A and IL-6 cytokines were also significantly reduced in lower concentrations of simvastatin (10 μM) compared to controls (p = 0.018; p = 0.04) and compared to the standard drug (p = 0.007; p = 0.0001). The results also showed that only RA patients with severe disease (DAS28 >5.1 and CDAI >22) had poor response to simvastatin in reducing cytokines levels, mainly for IL-17A and IL-22 cytokines (p = 0.03; p = 0.039, respectively).
  
  
  CONCLUSIONS
  The RA patients in clinical remission, mild or moderate had lower levels of all cytokines analyzed after simvastatin treatment, showing that these patients have better response to treatment. Our findings suggest that the simvastatin therapy modulates different cytokines in a dose dependent manner and its effect is associated with stratification of patients according to disease activity.
authors.affiliation: Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, Brazil.
authors.forename: Michelly Cristiny
authors.initials: MC
authors.lastname: Pereira
authors.forename: Pablo Ramon Gualberto
authors.initials: PR
authors.lastname: Cardoso
authors.forename: Laurindo Ferreira
authors.initials: LF
authors.lastname: Da Rocha
authors.forename: Moacyr Jesus Barreto Melo
authors.initials: MJ
authors.lastname: Rêgo
authors.forename: Sayonara Maria Calado
authors.initials: SM
authors.lastname: Gonçalves
authors.forename: Flaviana Alves
authors.initials: FA
authors.lastname: Santos
authors.forename: Marina Rocha
authors.initials: MR
authors.lastname: Galdino-Pitta
authors.forename: Andréa Tavares
authors.initials: AT
authors.lastname: Dantas
authors.forename: Ângela Luzia Branco Pinto
authors.initials: ÂL
authors.lastname: Duarte
authors.forename: Maira Galdino Da Rocha
authors.initials: MG
authors.lastname: Pitta
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin