Hydroxychloroquine exerts its immunomodulatory effect in systemic lupus erythematosus primarily by which mechanism?

• A Raising lysosomal pH, impairing antigen processing and Toll-like receptor signalling ✓
• B Inhibition of cyclooxygenase-2 in synovial macrophages
• C Blockade of the interleukin-6 receptor on B cells
• D Direct inhibition of DNA polymerase in autoreactive lymphocytes

Explanation

Hydroxychloroquine accumulates in lysosomes as a weak base, raising their pH. This impairs proteolytic processing of self antigens and blocks nucleic acid engagement of endosomal Toll-like receptors (TLR7 and TLR9), thereby dampening plasmacytoid dendritic cell interferon production central to SLE pathogenesis. It also reduces A cell activation and costimulation. Cyclooxygenase inhibition is the domain of NSAIDs and IL-6 receptor blockade belongs to biologics such as tocilizumab.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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