Elevated circulating levels of the interferon-gamma-induced chemokines are associated with disease activity and cutaneous manifestations in adult-onset Still's disease

Abstract

C-X-C motif chemokine 9 (CXCL9), CXCL10, and CXCL11 are produced in response to interferon-gamma (IFN-gamma) and trigger inflammation with the accumulation of activated lymphocytes. It appears that these chemokines could play a role in the pathogenesis of adult-onset Still's disease (AOSD). Therefore, we investigated the associations between the levels of these chemokine and clinical manifestations in patients with active AOSD. Serum levels of IFN-gamma, CXCL9, CXCL10 and CXCL11 were determined using enzyme-linked immunosorbent assays. IFN-gamma levels were higher in AOSD patients than in rheumatoid arthritis (RA) patients (p = 0.001) or healthy controls (HCs) (p = 0.032). AOSD patients also exhibited higher levels of CXCL9, CXCL10, and CXCL11 compared with RA patients (p < 0.001) and HCs (p < 0.001). In follow-up AOSD patients after treatment with corticosteroid, the levels of CXCL9, CXCL10 and CXCL11 fell significantly, whereas IFN-gamma levels were not significantly different. On immunohistochemistry, the percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples from AOSD patients than in those from normal control (p = 0.012), eczema (p = 0.019), and psoriasis (p = 0.009) groups. Levels of the IFN-gamma-induced chemokines, CXCL9, CXCL10 and CXCL11, were elevated and correlated with several disease activity markers. These interferon-gamma-induced chemokines may contribute to inflammatory responses and skin manifestations in AOSD.