Tobar Cindy Gabriela Rivera, Urmendiz Yisel Del Mar Morales, Vallejo Marcela Alejandra, Manquillo Diego Felipe, Castaño Victoria Eugenia Niño, Caicedo Ana Isabel Ospina, Tobar Leydy Lorena Mendoza, Vargas Jimmy Alexander Guerrero, Cuellar Rosa Amalia Dueñas
Grupo de Investigación en Inmunología y Enfermedades Infecciosas, Programa de Medicina, Departamento de Patología, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Colombia.
Grupo de Investigación en Salud, Programa de Medicina, Departamento de Medicina Interna, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Colombia.
J Venom Anim Toxins Incl Trop Dis. 2024 Sep 16;30:e20230064. doi: 10.1590/1678-9199-JVATITD-2023-0064. eCollection 2024.
Pathophysiological mechanisms of rheumatoid arthritis arise because of a proinflammatory environment, generated by the interaction of autoreactive lymphocytes and proinflammatory mediators. Current strategies to mitigate the progression of the disease produce adverse effects, so there is a need for new therapeutic strategies and molecular targets to treat this disease. In this context, evidence suggests that scorpion venoms could modulate the immune response and some important cellular mechanisms of pharmacological interest. To evaluate the immunomodulatory effect of the venom of sp. (a possible new species close to ) peripheral blood mononuclear cells of women diagnosed with RA were compared to cells of a control group.
A case-control study was conducted with a sample of 10 women with a confirmed diagnosis of RA and controls matched by sex and age. The cytotoxicity of the venom was evaluated to find sublethal concentrations of the venom, and subsequently, their immunomodulatory capacity in terms of percentage of proliferation, cell activation, and cytokines production.
the venom of sp. produced a decrease in the percentage of proliferation in the CD3, CD3CD4, and CD3CD8 cell subpopulations of RA patients and healthy controls, at concentrations of 252 and 126 µg/mL. However, the venom did not induce significant differences in the percentage of cell activation markers. The venom caused a decrease in IL-10 at a concentration of 252 µg/mL compared to untreated cells from patients and controls. The remaining cytokines did not show significant differences.
the venom of sp. is a potential source of molecules with immunomodulatory ability in CD4 and CD8 T lymphocytes. This result directs venom characterization studies to identify pharmacological targets with immunomodulatory capacity in T lymphocytes to enhance research in the treatment of autoimmune disorders such as RA.
类风湿性关节炎的病理生理机制源于自身反应性淋巴细胞与促炎介质相互作用产生的促炎环境。目前减轻该疾病进展的策略会产生不良反应,因此需要新的治疗策略和分子靶点来治疗这种疾病。在这种背景下,有证据表明蝎毒可以调节免疫反应以及一些具有药理学意义的重要细胞机制。为了评估蝎毒的免疫调节作用,将确诊为类风湿性关节炎的女性外周血单核细胞与对照组细胞进行了比较。
进行了一项病例对照研究,样本包括10名确诊为类风湿性关节炎的女性以及性别和年龄匹配的对照组。评估了蝎毒的细胞毒性以确定其亚致死浓度,随后,从增殖百分比、细胞活化和细胞因子产生方面评估了其免疫调节能力。
在浓度为252和126μg/mL时,蝎毒使类风湿性关节炎患者和健康对照组的CD3、CD3CD4和CD3CD8细胞亚群的增殖百分比降低。然而,蝎毒在细胞活化标志物百分比方面未诱导出显著差异。与患者和对照组未经处理的细胞相比,蝎毒在浓度为252μg/mL时使白细胞介素-10降低。其余细胞因子未显示出显著差异。
蝎毒是在CD4和CD8 T淋巴细胞中具有免疫调节能力的分子的潜在来源。这一结果引导蝎毒特性研究去鉴定在T淋巴细胞中具有免疫调节能力的药理学靶点,以加强对类风湿性关节炎等自身免疫性疾病治疗的研究。