Hydroxychloroquine in rheumatic autoimmune disorders and beyond

Area of Science:

• Immunology
• Pharmacology
• Cell Biology

Background:

• Hydroxychloroquine (HCQ) and chloroquine (CQ) are established antimalarial drugs with expanding therapeutic applications.
• HCQ is widely used for rheumatic autoimmune disorders (RADs) due to its favorable safety and efficacy profile.
• The precise molecular mechanisms underlying HCQ's actions in RADs remain incompletely elucidated.

Purpose of the Study:

• To review current knowledge on the molecular modes of action of HCQ and CQ.
• To explore the cellular pathways and mechanisms targeted by these drugs.
• To discuss the factors contributing to the side effects associated with HCQ and CQ.

Main Methods:

• Literature review of existing research on HCQ and CQ.
• Analysis of cellular pathways affected by these drugs, including endolysosomal functions, autophagy, and Toll-like receptor signaling.
• Examination of immune system alterations and their impact on pro-inflammatory cytokine production.

Main Results:

• HCQ and CQ inhibit multiple endolysosomal functions, including autophagy and Toll-like receptor activation.
• These drugs modulate calcium signaling pathways.
• Inhibition of these pathways leads to reduced pro-inflammatory cytokine production, a key feature of RADs.

Conclusions:

• HCQ and CQ exert their therapeutic effects by modulating fundamental cellular processes and immune responses.
• A comprehensive understanding of their molecular actions is essential for optimizing their use and managing potential side effects.
• The expanding therapeutic landscape for HCQ necessitates continued investigation into its mechanisms of action.