Siuchnińska Hanna, Minarowska Alina, Wasilewska Eliza
Occupational Therapy Center in Czersk ul Pomorska 10, 89-650 Czersk, Poland.
Department of Pulmonology, School of Public Health, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Jagiellońska 78, 10-357 Olsztyn, Poland.
Int J Mol Sci. 2025 Aug 28;26(17):8361. doi: 10.3390/ijms26178361.
Rheumatoid arthritis (RA) is a systemic autoimmune disease that, beyond joint destruction, contributes to neuropsychiatric symptoms such as depression, anxiety, and cognitive impairment. These symptoms are often underrecognized despite their major impact on quality of life. Accumulating evidence suggests that pro-inflammatory cytokines, particularly tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), play a key role in this neuroimmune interface. This narrative review examined 16 clinical studies evaluating the effects of biologic therapies targeting TNF-α and IL-6 on mental health outcomes in RA. The total study population comprised 9939 patients, including 2467 treated with TNF-α inhibitors and 7472 with IL-6 or IL-6 receptor inhibitors. TNF-α inhibitors were associated with improved depressive symptoms and emotional well-being. IL-6 inhibitors demonstrated similar psychiatric benefits, particularly in patients with elevated IL-6 levels. The findings highlight that biological therapies in RA may influence not only physical symptoms but also mental health, likely through modulation of neuroimmune pathways including blood-brain barrier permeability, microglial activation, and HPA axis regulation. Future research is needed to clarify these effects in populations stratified by psychiatric comorbidity and inflammatory biomarkers. Clinical implications: Incorporating psychiatric symptom screening and considering neuroinflammatory profiles may help guide the selection of biologic therapy in RA, particularly in patients with comorbid depression or fatigue.
类风湿性关节炎（RA）是一种全身性自身免疫性疾病，除了会导致关节破坏外，还会引发神经精神症状，如抑郁、焦虑和认知障碍。尽管这些症状对生活质量有重大影响，但往往未得到充分认识。越来越多的证据表明，促炎细胞因子，特别是肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6），在这种神经免疫界面中起关键作用。这篇叙述性综述考察了16项临床研究，评估了针对TNF-α和IL-6的生物疗法对类风湿性关节炎患者心理健康结果的影响。研究总人群包括9939名患者，其中2467名接受TNF-α抑制剂治疗，7472名接受IL-6或IL-6受体抑制剂治疗。TNF-α抑制剂与抑郁症状改善和情绪幸福感提高有关。IL-6抑制剂也显示出类似的精神方面益处，尤其是在IL-6水平升高的患者中。研究结果突出表明，类风湿性关节炎的生物疗法可能不仅影响身体症状，还会影响心理健康，这可能是通过调节神经免疫途径实现的，这些途径包括血脑屏障通透性、小胶质细胞激活和下丘脑-垂体-肾上腺（HPA）轴调节。未来需要开展研究，以阐明在按精神疾病共病情况和炎症生物标志物分层的人群中的这些影响。临床意义：纳入精神症状筛查并考虑神经炎症特征可能有助于指导类风湿性关节炎生物疗法的选择，特别是对于伴有抑郁或疲劳共病的患者。
