Molecule
IL-6 (Interleukin-6)
Upstream inducer of VEGF — overexpressed by clonal plasma cells
- Expression change
- Elevated
- Evidence level
- strong
- Targeted by
- Siltuximab (anti-IL-6, used in Castleman disease)
Role in pathogenesis
IL-6 is a pro-inflammatory cytokine elevated in POEMS syndrome. Single-cell RNA-Seq (Isshiki et al. 2022) showed that clonal plasma cells in POEMS overexpress IL-6 but NOT VEGF, positioning IL-6 as the upstream driver. IL-6 stimulates VEGF production by surrounding stromal and immune cells. Also drives systemic inflammation, osteosclerosis, and Castleman disease-like lymph node changes. Identified as a highly prognostic biomarker.