Disease activity and cytokine production in mitogen-stimulated peripheral blood mononuclear cells from patients with rheumatoid arthritis.

OBJECTIVE

To test whether there are differences in the levels and ratios of 6 pro- and 3 anti-inflammatory cytokines produced by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) subjects compared to controls.

SUBJECTS AND METHODS

79 participants (42 seropositive RA patients and 37 healthy controls) were enrolled in this study. The production levels in mitogen-stimulated PBMCs of the 6 proinflammatory cytokines (IFN-gamma, TNF-alpha, TNF-beta, IL-8, IL-17, IL-18) and 3 anti-inflammatory cytokines (IL-4, IL-10, IL-13) were assayed by ELISA using kits obtained from Immunotech SA. The ratios of pro- to anti-inflammatory cytokines were calculated for all participants.

RESULTS

There were significantly elevated levels of IL-8 and IL-10, and reduced levels of IFN-gamma, IL-4, and IL-17 in mitogen-stimulated PBMC culture supernatants of RA subjects compared to controls. Of the 18 pro-/anti-inflammatory cytokine ratios, 3 ratios (TNF-alpha/IL13, IL-8/IL-4 and IL-8/IL-13) were significantly higher in RA patients compared to controls; and 6 were higher in controls (IFN-gamma/IL-4; IFN-gamma/IL-10; IFN-gamma/IL-13; TNF-beta/IL10; IL-17/IL-10; IL-18/IL-10).

CONCLUSIONS

Activated PBMCs of RA patients, regardless of disease activity, showed higher-level production of IL-8 and IL-10 compared to controls; lower-level production of IFN-gamma, IL-4, and IL-17; and elevated ratios of TNF-alpha/IL-13, IL-8/IL-4 and IL-8/IL-13.