TNF and rheumatoid arthritis: Circulating cytokines (e.g., IL-1, IL-6, IL-12, tumor necrosis factor [TNF], interferon-γ, granulocyte–macrophage colony-stimulating factor), chemokines (e.g., monocyte chemotactic protein-1, macrophage inflammatory protein-1) and common markers of inflammation such as C-reactive protein have all been shown to increase progressively during the preclinical stages of RA, paralleling or even preceding the appearance and maturation of pathogenic autoantibodies (194–196).