Ene Corina Daniela, Tocut Milena, Tampa Mircea, Georgescu Simona Roxana, Matei Clara, Leulescu Iulia Maria Teodora, Nicolae Ilinca, Ene Cosmin
Department of Nephrology, 'Carol Davila' Nephrology Hospital, 010731 Bucharest, Romania.
Department of Nephrology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.
J Pers Med. 2024 Mar 10;14(3):295. doi: 10.3390/jpm14030295.
Research regarding the role of the IL-12 cytokine family in modulating immune and inflammatory responses is continuously evolving. In this study, the contribution of the p35 and p40 subunits as monomers (noted as IL-12p35 and IL-12p40) and heterodimers (noted as IL-12p70 or IL-12p35/p40) was analysed in the pathophysiology and progression of chronic spontaneous urticaria (CSU).
We conducted a longitudinal, case-control study involving 42 CSU cases and 40 control cases comprising adults without associated conditions. Serial measurements were performed to assess the serum levels of IL-12p70, IL-12p35, and IL-12p40 at the onset of the disease (pre-therapy phase) and 6 weeks after the initiation of the treatment (post-therapy phase).
During the pre-therapeutic phase of CSU, elevated serum levels of IL-12 cytokine subtypes were detected compared to the control group. The relationship between IL-12 profiles and the course of CSU highlighted the pro-inflammatory role of IL-12p70 and the anti-inflammatory role of IL-12p35. Significant correlations were observed between IL-12p70 levels and the duration of the disease, as well as between IL-12 and the effectiveness of H1-antihistamines.
The molecular background for the pleiotropic activities mediated by IL-12-derived cytokines in patients with CSU lies in the strict regulation of the production, signalling pathways, and cytokine-specific influences on the same pathophysiological events. The results of the present study suggest that the superficial layers of the skin serve as a cellular source of IL-12, a cytokine produced through antigenic stimulation. In patients with CSU, we identified independent, additive, or divergent functions of IL-12p70, IL-12p35, and IL-12p40, all relevant to systemic inflammation. These findings prove that the prototype programming of IL-12 is abnormal in CSU.
关于白细胞介素 - 12细胞因子家族在调节免疫和炎症反应中作用的研究不断发展。在本研究中,分析了p35和p40亚基作为单体(分别记为白细胞介素 - 12p35和白细胞介素 - 12p40)和异二聚体(分别记为白细胞介素 - 12p70或白细胞介素 - 12p35 / p40)在慢性自发性荨麻疹(CSU)的病理生理学和病程中的作用。
我们进行了一项纵向病例对照研究,涉及42例CSU病例和40例对照病例,对照病例为无相关疾病的成年人。在疾病发作时(治疗前阶段)和治疗开始6周后(治疗后阶段)进行系列测量,以评估血清中白细胞介素 - 12p70、白细胞介素 - 12p35和白细胞介素 - 12p40的水平。
在CSU的治疗前阶段,与对照组相比,检测到血清中白细胞介素 - 12细胞因子亚型水平升高。白细胞介素 - 12谱与CSU病程之间的关系突出了白细胞介素 - 12p70的促炎作用和白细胞介素 - 12p35的抗炎作用。观察到白细胞介素 - 12p70水平与疾病持续时间之间以及白细胞介素 - 12与H1抗组胺药疗效之间存在显著相关性。
CSU患者中白细胞介素 - 12衍生细胞因子介导的多效性活动的分子背景在于对产生、信号通路以及细胞因子对相同病理生理事件的特异性影响的严格调控。本研究结果表明,皮肤表层是白细胞介素 - 12的细胞来源,白细胞介素 - 12是通过抗原刺激产生的一种细胞因子。在CSU患者中,我们确定了白细胞介素 - 12p70、白细胞介素 - 12p35和白细胞介素 - 12p40的独立、相加或不同功能,所有这些功能都与全身炎症有关。这些发现证明CSU中白细胞介素 - 12的原型编程异常。