Th1/Th17 Cytokine Profile is Induced by Macrophage Migration Inhibitory Factor in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients

Background: Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that plays a crucial role as a regulator of the innate and adaptive immune responses and takes part in the destructive process of the joint in rheumatoid arthritis (RA) by promoting angiogenesis and inducing proinflammatory cytokines and matrix metalloproteinases (MMP). We evaluated if recombinant human MIF (rhMIF) induces the production of TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-17A, and IL- 17F in peripheral blood mononuclear cells (PBMC) from RA patients and control subjects (CS). Methods: The PBMC from RA patients and CS were stimulated for 24 hours with combinations of LPS, rhMIF or the MIF antagonist ISO-1. Cytokine profiles were measured using a multiplex immunoassay and, macrophage migration inhibitory factor (MIF) was determined by ELISA kit. Results: The PBMC of CS and RA produced Th1 and Th17 cytokines under stimulation with rhMIF, however, this effect was higher in the cells of RA patients. The rhMIFstimulated PBMC from RA patients produced higher levels of Th1 and Th17 cytokines in comparison with unstimulated cells: TNF-α (538.81 vs. 5.02 pg/mL, p<0.001), IFN-γ (721.90 vs. 8.40 pg/mL, p<0.001), IL-1β (150.14 vs. 5.17 pg/mL, p<0.05), IL-6 (19769.70 vs. 119.85 pg/mL, p<0.001), IL-17A (34.97 vs. 0.90 pg/mL, p<0.01) and IL-17F (158.43 vs. 0.92 pg/mL, p<0.001). Conclusion: These results highlight the potential role of MIF in the establishment of the chronic inflammatory process in RA via Th1 and Th17 cytokine profile induction and provide new evidence of the role of MIF to stimulate the IL-17A and IL-17F expression in PBMC from RA and CS.