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监测乌司奴单抗治疗中炎症相关基因——白细胞介素-6、白细胞介素-8和干扰素-γ的表达:初步结果

Expression of genes related to inflammation - IL-6, IL-8, and IFN-γ in monitoring ustekinumab therapy: preliminary results.

作者信息

Kruszniewska-Rajs Celina, Krawczyk Agata, Gola Joanna, Wcisło-Dziadecka Dominika, Strzalka-Mrozik Barbara

机构信息

Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland.

Department of Nutrigenomic and Bromatology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Poland.

出版信息

Postepy Dermatol Alergol. 2022 Dec;39(6):1040-1047. doi: 10.5114/ada.2022.122602. Epub 2022 Dec 22.

Abstract

INTRODUCTION

Psoriasis is classified as an inflammatory and autoimmune disease. Changes in the concentration profile of some cytokines, such as interleukin-12 (IL-12), IL-23, and IL-17, play a key role in its pathogenesis. IL-6, IL-8 and interferon- γ (IFN-γ) are also hallmark cytokines in a psoriatic cytokine network. Cytokine-blocking drugs, which are a part of the inflammatory cascade, are now increasingly popular. One of them is ustekinumab, directed against IL-12 and IL-23, but also indirectly against other interleukins, which take part in the inflammatory reaction. Due to the complexity of inflammation pathways, new molecular markers are still being sought. Regardless of the type of therapy used, they allow to determine its effectiveness, signal the lack or loss of sensitivity to treatment.

AIM

To evaluate the expression profile of genes related to the inflammatory reaction - IL-6, IL-8, and IFN-γ - in patients with psoriasis, depending on the duration of ustekinumab therapy.

MATERIAL AND METHODS

The material for the study was the PBMCs of 14 patients suffering from psoriasis who were treated with ustekinumab. Monitoring was performed after 16, 28, and 40 weeks of therapy. The gene expression of IL-6, IL-8, and IFN-γ was measured using the RT-qPCR method.

RESULTS

There was a statistically significant increase in the expression of IL-6 and IFN-γ genes in psoriasis patients, depending on the duration of ustekinumab therapy.

CONCLUSIONS

The increase in mRNA copy numbers of the pro-inflammatory IL-6 and IFN-γ genes in the following weeks of therapy may suggest that patients treated with ustekinumab may progressively develop resistance to biological treatment.

摘要

引言

银屑病被归类为一种炎症性自身免疫性疾病。某些细胞因子浓度谱的变化,如白细胞介素 - 12(IL - 12)、IL - 23和IL - 17,在其发病机制中起关键作用。IL - 6、IL - 8和干扰素 - γ(IFN - γ)也是银屑病细胞因子网络中的标志性细胞因子。作为炎症级联反应一部分的细胞因子阻断药物现在越来越受欢迎。其中之一是乌司奴单抗,它针对IL - 12和IL - 23,也间接针对参与炎症反应的其他白细胞介素。由于炎症途径的复杂性,仍在寻找新的分子标志物。无论使用何种治疗方法,它们都能确定其有效性,提示对治疗缺乏敏感性或敏感性丧失。

目的

根据乌司奴单抗治疗的持续时间,评估银屑病患者中与炎症反应相关基因——IL - 6、IL - 8和IFN - γ——的表达谱。

材料和方法

研究材料为14例接受乌司奴单抗治疗的银屑病患者的外周血单核细胞(PBMC)。在治疗16、28和40周后进行监测。使用RT - qPCR方法测量IL - 6、IL - 8和IFN - γ的基因表达。

结果

根据乌司奴单抗治疗的持续时间,银屑病患者中IL - 6和IFN - γ基因的表达有统计学显著增加。

结论

在治疗的接下来几周中,促炎IL - 6和IFN - γ基因的mRNA拷贝数增加可能表明接受乌司奴单抗治疗的患者可能会逐渐产生对生物治疗的耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d86a/9837596/281f0dd66feb/PDIA-39-48902-g001.jpg

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