Psoriasis is a chronic disorder characterized by a complex interplay between keratinocytes and inflammatory mediators. In a previous study, we evaluated diacerein's ability to diminish interleukin (IL)-1's proinflammatory effects on cultured primary human keratinocytes. In this study, we evaluated diacerein's ability to diminish the inflammatory effects of a cytokine mixture (CM) consisting of IL-17A, IL-22, oncostatin M, IL-1A, and tumor necrosis factor (TNF)-alpha on cultured primary human keratinocytes. These five cytokines have been previously shown to induce an in vivo-equivalent cell culture psoriasis model. We also evaluated diacerein's anti-inflammatory effects in comparison to and in combination with infliximab, a TNF-alpha inhibitor currently used in the treatment of psoriasis. We found 81 genes that were significantly (P < 0.05) dysregulated by CM compared to medium control. All three treatment groups (diacerein alone, infliximab alone, and diacerein plus infliximab) diminished the effects of CM on these genes, with the greatest effect seen with diacerein plus infliximab. Using enzyme-linked immunosorbent assay method on cell culture supernatant, we determined the protein concentration for five genes (IL-19, IL-6, CSF3, S100A8, and NAP-2) significantly (P < 0.05) upregulated by CM at the gene level. Diacerein alone diminished the effect of CM on the protein concentration of two genes, whereas diacerein plus infliximab diminished the effect of CM on the protein concentration of all the five genes. Based on these results, we conclude that diacerein alone or in combination with infliximab may have a therapeutic role in psoriasis by downregulating key inflammatory mediators.

中文翻译：

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双醋瑞因单独使用以及与英夫利昔单抗联合使用可抑制角质形成细胞中 IL-17A、IL-22、制瘤素 M、IL-1A 和 TNF-α 的联合促炎作用：银屑病的潜在治疗选择


牛皮癣是一种慢性疾病，其特征是角质形成细胞和炎症介质之间复杂的相互作用。在之前的一项研究中，我们评估了双醋瑞因减少白细胞介素 (IL)-1 对培养的原代人角质形成细胞的促炎作用的能力。在这项研究中，我们评估了双醋瑞因减轻由 IL-17A、IL-22、制瘤素 M、IL-1A 和肿瘤坏死因子 (TNF)-α 组成的细胞因子混合物 (CM) 对培养的原代人类的炎症影响的能力。角质形成细胞。这五种细胞因子先前已被证明可诱导体内等效细胞培养牛皮癣模型。我们还评估了双醋瑞因与英夫利昔单抗（目前用于治疗牛皮癣的 TNF-α 抑制剂）的比较和联合用药的抗炎作用。我们发现与培养基对照相比，CM 显着失调 ( P < 0.05) 81 个基因。所有三个治疗组（单独双醋瑞因、单独英夫利昔单抗和双醋瑞因加英夫利昔单抗）均减弱了 CM 对这些基因的影响，其中双醋瑞因加英夫利昔单抗的效果最大。采用酶联免疫吸附法对细胞培养上清液进行检测，测定了 CM 显着上调的 5 个基因（IL-19、IL-6、CSF3、S100A8 和 NAP-2）的蛋白浓度（ P < 0.05）。等级。单独的双醋瑞因减弱了 CM 对两个基因的蛋白质浓度的影响，而双醋瑞因加英夫利昔单抗则减弱了 CM 对所有五个基因的蛋白质浓度的影响。基于这些结果，我们得出结论，双醋瑞因单独使用或与英夫利昔单抗联合使用可能通过下调关键炎症介质对银屑病具有治疗作用。