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

Lupus - Tập 21 Số 8 - Trang 830-835 - 2012
Rohan Willis1, Alan M. Seif1, Gerald McGwin2, L-A Martinez-Martinez1, Emma Camarero González3,1, Neha Dang1, Elizabeth Papalardo1, J. LIU2, LM Vilá4, John D. Reveille5, GS Alarcón2, Silvia S. Pierangeli1
1University of Texas Medical Branch, Galveston, USA
2University of Alabama at Birmingham USA
3Internal Medicine
4University of Puerto Rico Medical Sciences Campus, San Juan, USA
5University of Texas-Houston Health Sciences Center, Houston, USA

Tóm tắt

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.

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