Immunomodulatory drugs regulate HMGB1 release from activated human monocytes

Area of Science:

• Immunology
• Rheumatology
• Pharmacology

Background:

• High-mobility group box 1 (HMGB1) is implicated in inflammatory diseases, with antagonists showing preclinical promise.
• No HMGB1-specific targeted therapies are currently approved for clinical use.

Purpose of the Study:

• To investigate if established antirheumatic drugs inhibit HMGB1 release from activated human monocytes.
• To explore the mechanism of HMGB1 inhibition by these drugs.

Main Methods:

• Peripheral blood monocytes from healthy donors were stimulated with LPS and IFNγ.
• Monocyte cultures were treated with various antirheumatic drugs (dexamethasone, cortisone, chloroquine, gold sodium thiomalate, methotrexate, colchicine, etanercept, anakinra).
• HMGB1 and TNF release were measured using ELISPOT assays; intracellular HMGB1 was assessed via immunostaining.

Main Results:

• Dexamethasone, gold sodium thiomalate, and chloroquine significantly inhibited extracellular HMGB1 release in a dose-dependent manner.
• Dexamethasone treatment resulted in intracellular HMGB1 retention.
• TNF production was downregulated by dexamethasone, chloroquine, and etanercept.

Conclusions:

• Dexamethasone, gold sodium thiomalate, and chloroquine inhibit HMGB1 release from activated monocytes.
• These drugs may exert their anti-inflammatory effects, in part, by modulating HMGB1 secretion.
• Further investigation into these drugs as potential HMGB1-targeted therapies for inflammatory conditions is warranted.