Immunosuppression by hydroxychloroquine: mechanistic proof in in vitro experiments but limited systemic activity in a randomized placebo-controlled clinical pharmacology study
Abstract
Based on its wide range of immunosuppressive properties, hydroxychloroquine (HCQ) is used for the treatment of several autoimmune diseases. Limited literature is available on the relationship between HCQ concentration and its immunosuppressive effect. To gain insight in this relationship, we performed in vitro experiments in human PBMCs and explored the effect of HCQ on T and B cell proliferation and Toll-like receptor (TLR)3/TLR7/TLR9/RIG-I-induced cytokine production. In a placebo-controlled clinical study, these same endpoints were evaluated in healthy volunteers that were treated with a cumulative dose of 2400 mg HCQ over 5 days. In vitro, HCQ inhibited TLR responses with IC50s > 100 ng/mL and reaching 100% inhibition. In the clinical study, maximal HCQ plasma concentrations ranged from 75 to 200 ng/mL. No ex vivo HCQ effects were found on RIG-I-mediated cytokine release, but there was significant suppression of TLR7 responses and mild suppression of TLR3 and TLR9 responses. Moreover, HCQ treatment did not affect B cell and T cell proliferation. These investigations show that HCQ has clear immunosuppressive effects on human PBMCs, but the effective concentrations exceed the circulating HCQ concentrations under conventional clinical use. Of note, based on HCQ’s physicochemical properties, tissue drug concentrations may be higher, potentially resulting in significant local immunosuppression. This trial is registered in the International Clinical Trials Registry Platform…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- Drug repositioning: a brief overview
- Cyclic nucleotide phosphodiesterases in Drosophila melanogaster
- Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation
- Current View on Green Tea Catechins Formulations, Their Interactions with Selected Drugs, and Prospective Applications for Various Health Conditions
- In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors Against Alzheimer’s Disease
- Development and In Vitro Evaluation of Controlled Release Viagra® Containing Poloxamer-188 Using Gastroplus™ PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.