Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients

Abstract

OBJECTIVES:Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients.METHODS:Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients.RESULTS:We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine.CONCLUSIONSOur in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication.

Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind, randomized comparison with pioglitazone

“…Interlukin-6 and C-reactive protein are two sensitive physiological markers of sub-clinical inflammation, associated with hyperglycemia, insulin resistance, and overt T2DM 13 . A recent study in SLE and RA patients has demonstrated that hydroxychloroquine inhibits production of interlukin-6 and other inflammatory markers 14 . Another long-term randomized trial on hydroxychloroquine in RA patients has demonstrated favorable effects of hydroxychloroquine on C-reactive protein showing a reduction of 20 mg/L from its initial value post 5 years of hydroxychloroquine use 15 .…”

Pharmacology of Chloroquine and Hydroxychloroquine

“…They reason that such concentrations are higher than those expected to be found clinically in the plasma [ 71 , 78 , 142 , 170 ]. For example, although hydroxychloroquine at a concentration of 1 × 10 −4 M/L affects IL-17 and other cytokine levels produced by the peripheral blood mononuclear cells of patients with RA and SLE in vitro, we are uncertain that this is a physiologic pathway [ 171 ]. In another example, signifi cant inhibition of immunoglobulin synthesis and secretion by rat plasma cells in vitro required concentration of 9 × 10 −4 M/L chloroquine [ 172 ].…”

Rheumatoid Arthritis: A Brief Overview of the Treatment

“…The eyes, in particular, can be affected when this drug is taken at high doses. Patients on this medication require routine consultation with an ophthalmologist [20]. …”