Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin …
M Shimizu, T Yokoyama, K Yamada, H Kaneda… - …, 2010 - academic.oup.com
M Shimizu, T Yokoyama, K Yamada, H Kaneda, H Wada, T Wada, T Toma, K Ohta…
Rheumatology, 2010•academic.oup.comObjectives. To compare the pro-inflammatory cytokine profiles and the cytokine kinetics in
patients with secondary macrophage activation syndrome (MAS) due to systemic-onset
juvenile idiopathic arthritis (s-JIA) and in both active and inactive disease states of s-JIA (but
no MAS), with those demonstrated in EBV-induced haemophagocytic lymphohistiocytosis
(HLH) and Kawasaki disease (KD), and to investigate the significance of IL-18 in the
pathogenesis of s-JIA. Methods. Five patients with MAS complicating s-JIA (MAS/s-JIA), 10 …
patients with secondary macrophage activation syndrome (MAS) due to systemic-onset
juvenile idiopathic arthritis (s-JIA) and in both active and inactive disease states of s-JIA (but
no MAS), with those demonstrated in EBV-induced haemophagocytic lymphohistiocytosis
(HLH) and Kawasaki disease (KD), and to investigate the significance of IL-18 in the
pathogenesis of s-JIA. Methods. Five patients with MAS complicating s-JIA (MAS/s-JIA), 10 …
Abstract
Objectives. To compare the pro-inflammatory cytokine profiles and the cytokine kinetics in patients with secondary macrophage activation syndrome (MAS) due to systemic-onset juvenile idiopathic arthritis (s-JIA) and in both active and inactive disease states of s-JIA (but no MAS), with those demonstrated in EBV-induced haemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD), and to investigate the significance of IL-18 in the pathogenesis of s-JIA.
Methods. Five patients with MAS complicating s-JIA (MAS/s-JIA), 10 with HLH due to EBV infection (EBV-HLH), 22 with KD and 28 healthy controls were analysed. Cytokine concentrations (IL-18, IL-6, neopterin and TNF-α receptor Types I and II) were quantified in serum by ELISA. Results were compared with clinical features of MAS/s-JIA, including ferritin concentrations.
Results. Serum IL-18 concentrations in MAS/s-JIA patients were significantly higher than those in EBV-HLH or KD patients (P < 0.05). Serum IL-6 concentrations in KD patients were significantly higher than those in EBV-HLH or MAS/s-JIA patients. Serum neopterin concentrations in EBV-HLH patients were significantly higher than those in MAS/s-JIA or KD patients. Serum IL-18 correlated positively with the following measurements of disease activity: CRP, ferritin, lactate dehydrogenase and other cytokines (P < 0.05). Serum concentrations of IL-18 in s-JIA patients remained elevated in the inactive phase of disease, whereas clinical parameters and other cytokines normalized.
Conclusions. IL-18 may be an important mediator in s-JIA. Although serum Il-18 concentrations correlated with markers of the disease activity, IL-18 concentrations remained elevated even when other markers of disease activity normalized. Serum IL-18 concentration may be a promising indicator of the disease activity. The cytokine release pattern in MAS/HLH is different among patients with different aetiologies. Monitoring the cytokine profile, including IL-18, may be useful for differentiation of MAS/HLH and evaluation of disease activity in s-JIA.
Oxford University Press