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.

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“…Shown are the representative results of three separate experiments with similar results. A B mokines promote the formation and development of atherosclerotic plaque as well as intravascular thrombi in patients with autoimmune diseases [35][36][37][38][39][40][41] . Although the involvement of cytokines and chemokines in the pathogenesis of atherosclerosis and autoimmune diseases is widely accepted, little is known about the underlying mechanisms or how these molecules trigger vascular inflammation and interact with autoantibodies.…”

Antimalarial drugs inhibit IFNα-enhanced TNFα and STAT4 expression in monocytes: Implication for systemic lupus erythematosus

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Cardiovascular Events in Systemic Lupus Erythematosus: Mechanisms for the Accelerated Development of Atherosclerosis, Diagnosis, Correction Capabilities

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