Intracellular Cytokine Production in ANCA-associated Vasculitis: Low Levels of Interleukin-10 in Remission Are Associated with a Higher Relapse Rate in the Long-term Follow-up

Background and Aims. Dysregulation of cell-mediated immune response likely plays a role in the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), but it has not yet been fully established. The aim of this study was to assess the intracellular cytokine production in patients with AAV at different stages of the disease, in particular, in relation to the long-term prognosis. Methods. We included 69 patients with AAV and 24 healthy controls. Using flow cytometry, the following intracellular cytokines (IC) were measured in all patients: interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-2 and interleukin-4 in CD3 + T cells and interleukin-10 (IL-10) and interleukin 12 (IL-12) in monocytes. Patients were then prospectively followed for a median of 43 months and cytokine production was related to the long-term prognosis. Results. When compared to healthy controls, increased IL-12 production was observed in AAV patients, both active (p < 0.01) and in remission (p < 0.05). In remission, increased IFN-gamma production was also found (p < 0.01). IL-10 production was higher inactive patients than in patients in remission (p < 0.05) but did not differ from controls. Patients in remission who developed a relapse during follow-up had significantly lower IL-10 production than those without relapse (p < 0.01). Results of this prospective study of IC production in AAV confirm findings of previous studies measuring circulating cytokine levels. Conclusions. Activation of the immune system in AAV patients is noticeable even in remission. Patients with AAV display increased IL-12 production, which seems to be counterbalanced by IL-10. Low IL-10 levels in remission are associated with a higher relapse rate in the long-term follow-up. (C) 2009 IMSS. Published by Elsevier Inc.