Fluvoxamine modulates interferon and inflammatory gene signatures in immune cell lines: an in silico transcriptomic...

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by chronic inflammation and dysregulated interferon (IFN) signaling. Many patients remain refractory to existing treatments, underscoring the need for novel therapeutic approaches achievable through drug repurposing. Fluvoxamine, an antidepressant with anti-inflammatory and immunomodulatory properties, has not been systematically studied in SLE.

Differentially expressed genes (|Z| ≥ 2) were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Gene Set Enrichment Analysis (GSEA) was applied to assess pathway-level modulation of six hallmark SLE-related signatures.

Fluvoxamine induced cell line-specific transcriptomic changes. Jurkat and THP-1 cells showed strong enrichment of TNF-α/NF-κB signaling and regulation of apoptosis-related genes, while HEK293 and A549 cells displayed modulation of cytokine and fibrotic pathways, including NOS3 upregulation. U2OS cells exhibited prominent apoptotic signatures. Although hallmark interferon-α/γ responses were modestly altered at the pathway level, canonical interferon-stimulated genes (e.g. IFI44L, ISG15, MX1) were not significantly downregulated in immune-derived lines. Overall, TNF-α/NF-κB activation and apoptosis emerged as the most consistently affected pathways across models.

This integrative transcriptomic study supports fluvoxamine as a candidate immunomodulator with potential relevance for SLE, particularly through modulation of NF-κB and apoptotic pathways. These findings provide a mechanistic rationale for further investigation of sigma-1 receptor-targeting agents in autoimmune diseases.