Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort

Lupus. 2012 Jul;21(8):830-5. doi: 10.1177/0961203312437270. Epub 2012 Feb 17.


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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Biomarkers / blood
  • CD40 Ligand / blood
  • CD40 Ligand / drug effects
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / drug effects
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / drug effects
  • Cohort Studies
  • Cytokines / blood*
  • Cytokines / drug effects
  • Female
  • Humans
  • Hydroxychloroquine / pharmacology
  • Hydroxychloroquine / therapeutic use*
  • Interferon-alpha / blood
  • Interferon-alpha / drug effects
  • Interleukin-1beta / blood
  • Interleukin-1beta / drug effects
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Interleukin-8 / drug effects
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / ethnology
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / drug effects
  • United States
  • Young Adult


  • Antirheumatic Agents
  • Biomarkers
  • Chemokine CCL2
  • Chemokine CXCL10
  • Cytokines
  • Interferon-alpha
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Tumor Necrosis Factor-alpha
  • CD40 Ligand
  • Hydroxychloroquine