Systemic juvenile idiopathic arthritis (sJIA) is a childhood rheumatic disease of unknown origin. Dysregulated innate immunity is implicated in disease pathology. We investigated if IL-1 inhibition affects circulating cytokines and monocyte gene expression. CD14+ monocytes from patients in the RAPPORT trial were analyzed by RT-PCR for expression of IL1B and transcription factors associated with monocyte activation. Serum IL-1ra decreased with treatment, and IL-18BP transiently increased. Serum levels of IL-1β, IL-6, IL-10 and IL-18 were unchanged. IRF5 and STAT6 were decreased, and PPARG was increased, independent of clinical response, and may represent a skew toward a PPARG-driven M2-like phenotype. IL1B expression was decreased in early clinical responders. A transient increase in STAT1, and a decrease in SOCS1 preceded the reduction in IL1B in early clinical responders. Changes in IL1B/STAT1/SOCS1 could be associated with crosstalk between IL-1 and IFN pathways in sJIA. These transcriptional changes might be useful as drug response biomarkers.

中文翻译：

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系统性幼年特发性关节炎中单核细胞激活表型中的白细胞介素-1：白细胞介素-1抑制剂rilonacept的临床试验观察结果。

系统性幼年特发性关节炎（sJIA）是一种来源不明的儿童风湿病。先天免疫力失调与疾病病理学有关。我们调查了IL-1抑制是否影响循环细胞因子和单核细胞基因表达。通过RT-PCR分析了RAPPORT试验中患者的CD14 +单核细胞中IL1B的表达和与单核细胞激活相关的转录因子。血清IL-1ra随治疗而降低，IL-18BP短暂升高。血清IL-1β，IL-6，IL-10和IL-18水平未改变。IRF5和STAT6减少，而PPARG增加，与临床反应无关，并且可能代表着偏向于PPARG驱动的M2样表型。在早期临床应答者中IL1B表达降低。STAT1的瞬时增加，在早期临床应答者中，SOCS1的降低先于IL1B的降低。IL1B / STAT1 / SOCS1的变化可能与sJIA中IL-1和IFN途径之间的串扰有关。这些转录变化可用作药物反应生物标记。