Bikker A, van Woerkom J M, Kruize A A, Wenting-van Wijk M, de Jager W, Bijlsma J W J, Lafeber F P J G, van Roon J A G
University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
Arthritis Rheum. 2010 Apr;62(4):969-77. doi: 10.1002/art.27318.
To study the expression levels and immunostimulatory capacities of interleukin-7 (IL-7) in primary Sjögren's syndrome.
Labial salivary gland (LSG) IL-7 expression was determined by immunohistochemistry, using a quantitative scoring system, in 30 patients with sicca syndrome: 15 patients with primary Sjögren's syndrome (SS) and 15 patients with non-SS sicca syndrome. The correlation of IL-7 expression in LSGs with parameters of local and peripheral disease was studied, and serum and salivary IL-7 levels were determined. Additionally, the effects of IL-7 on cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with primary SS were determined in vitro by Luminex multicytokine assay and compared with the effects in control subjects.
The expression of IL-7 in LSGs was higher in patients with primary SS compared with that in patients with non-SS sicca syndrome. IL-7 was observed primarily in the vicinity of lymphocytic infiltrates. Salivary IL-7 levels in patients with primary SS were higher than those in control subjects. In all 30 patients with sicca syndrome, IL-7 expression in LSGs correlated with parameters of both local and peripheral disease. Furthermore, IL-7 stimulated T cell-attracting and T cell-differentiating cytokines (monokine induced by interferon-gamma [IFNgamma], IFNgamma-inducible 10-kd protein, IL-12, and IL-15), as well as Th1 (IFNgamma), Th2 (IL-4), Th17 (IL-17A), proinflammatory (tumor necrosis factor alpha and IL-1alpha), and regulatory (IL-10 and IL-13) cytokine production by PBMCs. All of these cytokines were previously shown to be associated with primary SS. The IL-7-induced increase in IL-10 production in patients with primary SS was reduced compared with that in control subjects.
The correlation between LSG IL-7 expression and (local) disease parameters in primary SS as well as the IL-7-mediated induction of inflammatory cytokines indicate that IL-7 might contribute to the immunopathology of primary SS.
研究白细胞介素-7（IL-7）在原发性干燥综合征中的表达水平及免疫刺激能力。
采用定量评分系统，通过免疫组织化学法检测30例干燥综合征患者唇腺中IL-7的表达：15例原发性干燥综合征（SS）患者和15例非SS干燥综合征患者。研究唇腺中IL-7表达与局部及外周疾病参数的相关性，并测定血清和唾液中IL-7水平。此外，通过Luminex多细胞因子检测法体外测定IL-7对原发性SS患者外周血单个核细胞（PBMC）细胞因子产生的影响，并与对照组进行比较。
与非SS干燥综合征患者相比，原发性SS患者唇腺中IL-7的表达更高。IL-7主要在淋巴细胞浸润附近观察到。原发性SS患者的唾液IL-7水平高于对照组。在所有30例干燥综合征患者中，唇腺中IL-7的表达与局部和外周疾病参数均相关。此外，IL-7刺激PBMC产生吸引T细胞和分化T细胞的细胞因子（γ干扰素诱导的单核因子[IFNγ]、IFNγ诱导的10-kd蛋白、IL-12和IL-15），以及Th1（IFNγ）、Th2（IL-4）、Th17（IL-17A）、促炎（肿瘤坏死因子α和IL-1α）和调节（IL-10和IL-13）细胞因子。所有这些细胞因子此前均被证明与原发性SS相关。与对照组相比，原发性SS患者中IL-7诱导的IL-10产生增加有所减少。
原发性SS中唇腺IL-7表达与（局部）疾病参数之间的相关性以及IL-7介导的炎性细胞因子诱导表明，IL-7可能参与原发性SS的免疫病理过程。
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