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Pyroptosis: the potential eye of the storm in adult-onset Still’s disease

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Abstract

Pyroptosis, a form of programmed cell death with a high pro-inflammatory effect, causes cell lysis and leads to the secretion of countless interleukin-1β (IL-1β) and IL-18 cytokines, resulting in a subsequent extreme inflammatory response through the caspase-1-dependent pathway or caspase-1-independent pathway. Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease with extensive disease manifestations and severe complications such as macrophage activation syndrome, which is characterized by high-grade inflammation and cytokine storms regulated by IL-1β and IL-18. To date, the pathogenesis of AOSD is unclear, and the available therapy is unsatisfactory. As such, AOSD is still a challenging disease. In addition, the high inflammatory states and the increased expression of multiple pyroptosis markers in AOSD indicate that pyroptosis plays an important role in the pathogenesis of AOSD. Accordingly, this review summarizes the molecular mechanisms of pyroptosis and describes the potential role of pyroptosis in AOSD, the therapeutic practicalities of pyroptosis target drugs in AOSD, and the therapeutic blueprint of other pyroptosis target drugs.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 82203932, No. 82073449, No. 82203930, No. 82001738, and No. 82003363) and the Natural Science Foundation of Hunan Province, China (No.2023JJ30790).

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  1. Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Xinglan He, Ruixuan You, Yaqian Shi, Zhuotong Zeng, Bingsi Tang, Jiangfan Yu & Rong Xiao

  2. Hunan Key Laboratory of Medical Epigenetics, Department of Dermatology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Xinglan He, Ruixuan You, Yaqian Shi, Zhuotong Zeng, Bingsi Tang, Jiangfan Yu & Rong Xiao

  3. Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China

    Yangfan Xiao

  4. Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China

    Yangfan Xiao

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Contributions

HXL: data curation, writing—original draft, formal analysis. YRX, SYQ, ZZT, TBS, and Y.JF: formal analysis, XYF and XR: funding acquisition, writing—review and editing.

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He, X., You, R., Shi, Y. et al. Pyroptosis: the potential eye of the storm in adult-onset Still’s disease. Inflammopharmacol 31, 2269–2282 (2023). https://doi.org/10.1007/s10787-023-01275-0

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