Our objective was to analyse the relationship between circulating cytokines, autoantibodies, acute phase reactants, and disease
activity in DMARDs-na¨ıve rheumatoid arthritis (RA) patients (n = 140). All cytokines were significantly higher in the RA cohort
than in healthy controls. Moderate-to-strong positive intercorrelations were observed between Th1/Th2/macrophage/fibroblastderived
cytokines. RF correlated significantly with IL-1β, IL-2, IL-4, IL-10, IL-12, G-CSF, GM-CSF, IFN-γ, and TNF (P < .0001),
and aCCP and aMCV with IL-1β, IL-2, IL-4, and IL-10 (P < .0002), while IL-6 correlated best with the acute phase reactants,
CRP, and SAA (P < .0001). In patients with a DAS28 score of ≥5.1, IFN-γ, IL-1β, IL-1Ra, TNF, GM-CSF, and VEGF were
significantly correlated (P < .04–.001) with high disease activity (HDA). Circulating cytokines in RA reflect a multifaceted increase
in immune reactivity encompassing Th1 and Th2 cells, monocytes/macrophages, and synovial fibroblasts, underscored by strong correlations between these cytokines, as well as their relationships with RF, aCCP, and aMCV, with some cytokines showing promise as biomarkers of HDA.