The relationship between inflammation and multiple myeloma: insights into alterations and prognostic value.

Multiple myeloma (MM) is an inflammation-driven plasma cell malignancy influenced by the bone marrow microenvironment. Dysregulated cytokine networks and neuroimmune factors may contribute to disease progression and extramedullary disease (EMD), a high-risk variant with poor prognosis. Plasma levels of 13 cytokines (IFN-γ, IL-1β, IL-2, IL-3, IL-6, IL-8, IL-9, IL-10, IL-17A, MCP-1, MIP-1α, TGF-α, TNF-α) and PACAP-38 - wich is an antiinflammatory neuropeptide-were measured in 48 MM patients and 10 healthy controls using ELISA and Luminex assays. MM patients exhibited elevated IFN-γ, IL-10, MCP-1 and reduced IL-17A, TGF-α compared to controls. Active disease correlated with higher IL-10 and TNF-α, while EMD showed marked increases in IFN-γ, IL-10, MCP-1, PACAP-38 and decreased TGF-α. IL-6, IL-10, IL-9, IL-17A, and TGF-α were associated with progression-free survival. PACAP-38 correlated positively with IL-10 and negatively with MCP-1 and MIP-1α. MM and EMD are characterized by distinct inflammatory and neuropeptide profiles with prognostic relevance. Integrating these biomarkers into risk models may improve stratification and guide personalized therapy. Larger studies are needed to validate clinical utility.