title: Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort.
abstract: OBJECTIVE
  We sought to determine the effect of hydroxychloroquine therapy on the levels proinflammatory/prothrombotic markers and disease activity scores in patients with systemic lupus erythematosus (SLE) in a multiethnic, multi-center cohort (LUMINA).
  
  
  METHODS
  Plasma/serum samples from SLE patients (n = 35) were evaluated at baseline and after hydroxychloroquine treatment. Disease activity was assessed using SLAM-R scores. Interferon (IFN)-α2, interleukin (IL)-1β, IL-6, IL-8, inducible protein (IP)-10, monocyte chemotactic protein-1, tumor necrosis factor (TNF)-α and soluble CD40 ligand (sCD40L) levels were determined by a multiplex immunoassay. Anticardiolipin antibodies were evaluated using ELISA assays. Thirty-two frequency-matched plasma/serum samples from healthy donors were used as controls.
  
  
  RESULTS
  Levels of IL-6, IP-10, sCD40L, IFN-α and TNF-α were significantly elevated in SLE patients versus controls. There was a positive but moderate correlation between SLAM-R scores at baseline and levels of IFN-α (p = 0.0546). Hydroxychloroquine therapy resulted in a significant decrease in SLAM-R scores (p = 0.0157), and the decrease in SLAM-R after hydroxychloroquine therapy strongly correlated with decreases in IFN-α (p = 0.0087).
  
  
  CONCLUSIONS
  Hydroxychloroquine therapy resulted in significant clinical improvement in SLE patients, which strongly correlated with reductions in IFN-α levels. This indicates an important role for the inhibition of endogenous TLR activation in the action of hydroxychloroquine in SLE and provides additional evidence for the importance of type I interferons in the pathogenesis of SLE. This study underscores the use of hydroxychloroquine in the treatment of SLE.
authors.affiliation: University of Texas Medical Branch, Galveston, USA.
authors.forename: R
authors.initials: R
authors.lastname: Willis
authors.forename: A M
authors.initials: AM
authors.lastname: Seif
authors.forename: G
authors.initials: G
authors.lastname: McGwin
authors.forename: L A
authors.initials: LA
authors.lastname: Martinez-Martinez
authors.forename: E B
authors.initials: EB
authors.lastname: González
authors.forename: N
authors.initials: N
authors.lastname: Dang
authors.forename: E
authors.initials: E
authors.lastname: Papalardo
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: L M
authors.initials: LM
authors.lastname: Vilá
authors.forename: J D
authors.initials: JD
authors.lastname: Reveille
authors.forename: G S
authors.initials: GS
authors.lastname: Alarcón
authors.forename: S S
authors.initials: SS
authors.lastname: Pierangeli
mesh_terms: D000293:Adolescent; D000328:Adult; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood / Q000187:drug effects; D018932:Chemokine CCL2 / Q000097:blood / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000097:blood / Q000187:drug effects; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000097:blood / Q000187:drug effects; D053583:Interleukin-1beta / Q000097:blood / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000187:drug effects; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy* / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects; D014481:United States; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D016207:Cytokines; D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D006886:Hydroxychloroquine