Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Int Immunopharmacol. 2023 Oct;123:110806. doi: 10.1016/j.intimp.2023.110806. Epub 2023 Aug 17.
Cholestatic pruritus is a distressful sensation that can cause a massive desire of scratching skin. Despite maximum medication therapy, some patients still experience pruritus. In this study, we evaluated the effect of infliximab on cholestatic pruritus induced in mice by bile duct ligation.
Twenty-four balb/c mice were randomly assigned to three groups; sham, control, and treatment. The bile duct ligation procedure was performed on mice in the control and treatment groups. After six days, mice in the treatment group received subcutaneous administration of infliximab, and the next day all mice were subjected to the scratching behavior test. Skin, dorsal root ganglia (DRG), and blood samples of mice were collected and evaluated by histopathological, molecular, and biochemical tests.
The scratching behavior has significantly decreased in mice with cholestasis after the administration of infliximab. The levels of TNFα, TNFR1, TNFR2, NF-κB, and IL-31were higher in control mice compared to sham. In addition, expression levels of TNFR1, NF-κB, and IL-31 were decreased in the treatment group compared to the controls in skin and DRG, while TNFR2 levels were decreased only in DRG.
Infliximab can block TNFα interaction with receptors and inhibit further inflammatory response. Also, our results suggested that infliximab can suppress IL-31 expression indirectly, which is a well-known cytokine in pruritus pathophysiology Infliximab can be a potential therapeutic approach in resistant pruritus in cholestatic disorders.
胆汁淤积性瘙痒是一种令人痛苦的感觉，会导致强烈的搔抓皮肤欲望。尽管进行了最大程度的药物治疗，仍有部分患者会出现瘙痒症状。在这项研究中，我们评估了英夫利昔单抗对胆管结扎诱导的小鼠胆汁淤积性瘙痒的影响。
24 只 BALB/c 小鼠随机分为三组：假手术组、对照组和治疗组。对照组和治疗组的小鼠进行胆管结扎手术。六天后，治疗组小鼠接受英夫利昔单抗皮下注射，次日所有小鼠均进行搔抓行为测试。采集小鼠皮肤、背根神经节（DRG）和血液样本，通过组织病理学、分子和生化测试进行评估。
胆汁淤积小鼠给予英夫利昔单抗后，搔抓行为显著减少。与假手术组相比，对照组小鼠的 TNFα、TNFR1、TNFR2、NF-κB 和 IL-31 水平更高。此外，与对照组相比，治疗组皮肤和 DRG 中 TNFR1、NF-κB 和 IL-31 的表达水平降低，而 DRG 中 TNFR2 的水平仅降低。
英夫利昔单抗可以阻断 TNFα 与受体的相互作用，抑制进一步的炎症反应。此外，我们的结果表明，英夫利昔单抗可以间接抑制 IL-31 的表达，IL-31 是瘙痒病理生理学中一种已知的细胞因子。英夫利昔单抗可能是胆汁淤积性疾病中难治性瘙痒的一种潜在治疗方法。
