IL-6 blockade reverses the abnormal STAT activation of peripheral blood leukocytes from rheumatoid arthritis patients.

Abstract Considering the interplay of multiple STATs in response to cytokines, we investigated how IL-6 and its blocking affect STAT signaling in rheumatoid arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab treatment and healthy donors (HDs) were cytokine-stimulated and STAT phosphorylation was analyzed by cytometry. RA patients had significantly fewer pSTAT1 +, pSTAT3 +, and pSTAT6 + monocytes and pSTAT5 + lymphocytes than HDs. After 24 weeks of treatment, percentages of IFNγ-induced pSTAT1 + and IL-10-induced pSTAT3 + monocytes in RA patients increased, reaching levels comparable to HDs. pSTAT1 + and pSTAT3 + cells correlated inversely with RA disease activity index and levels of pSTAT + cells at baseline were higher in patients with good EULAR response to tocilizumab. IFNγ-induced pSTAT1 + cells correlated inversely with memory T cells and anti-CCP levels. IL-10-induced pSTAT3 + cells correlated with Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory mechanisms through the correction of STAT1 and STAT3 activation status.