Patterns of circulatory and peripheral blood mononuclear cytokines in rheumatoid arthritis

An imbalance in pro- and anti-inflammatory cytokines is suggested to contribute to tissue damage in rheumatoid arthritis (RA). This study was aimed at investigating profiles of cytokines in circulation and cytokines produced by mitogen-stimulated peripheral blood mononuclear cells (PBMC) in RA patients and healthy controls, and to explore correlations of cytokines with disease activity. Our aim was to identify patterns of cytokine expression as possible indicators of disease activity. Levels of plasma cytokines and PBMC-secreted cytokines were estimated in 26 female RA patients and 28 controls. Five pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6, IL-17, IL-12) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were assayed in a multiplex ELISA. RA patients had significantly higher plasma levels of TNF-α, IL-12, and IL-4 compared to healthy controls. On the other hand, mitogen-activated PBMC secreted significantly higher levels of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-17, and IL-12, but lower levels of the anti-inflammatory cytokine IL-10 in RA compared to healthy subjects. The ratios TNF-α/IL-10, IFN-γ/IL-10, IL-17/IL-10, IL-12/IL-10, and IFN-γ/IL-13 were significantly higher in RA patients compared to healthy controls. The range and expression of cytokines were higher in PBMC than in the plasma in all the groups studied. Multivariate pattern analysis of eight cytokines revealed a prediction accuracy of 69% in differentiating RA patients from healthy controls, and of 73% in classifying patients as in remission or active RA. Our data suggest that it is worthwhile to explore ratios of pro- to anti-inflammatory cytokines produced by mitogen-stimulated PBMC in RA, and the use of multivariate cytokine pattern and algorithms for better delineation of this condition.