Unità Operativa Complessa di Patologia Clinica, Ospedale San Pietro Fatebenefratelli, 00189 Rome, Italy.
Department of Clinical Pathology, Santa Maria Goretti Hospital, 04100 Latina, Italy.
Int J Mol Sci. 2024 Jul 16;25(14):7762. doi: 10.3390/ijms25147762.
Skin is the forestage for a series of many-sided functions of tumor necrosis factor-alpha (TNF-α), a proinflammatory cytokine with staggering versatility and sizable implications for tissue homeostasis, immune responses, angiogenesis, apoptosis, local and systemic inflammation. An aberrant TNF-α-mediated crosstalk has been linked to the pathogenesis of acute and chronic skin inflammatory diseases, and indeed, TNF-α dysregulation can contribute to the development and progression of psoriasis, vitiligo, local damage following exposition to ultraviolet light radiations, cutaneous lupus erythematosus, and acne vulgaris. Therapies that target TNF-α are conspicuously used in the treatment of different skin disorders, aiming to modulate the in vivo immune functions triggered by many cutaneous cells, including keratinocytes, mast cells, or Langerhans cells, and reduce inflammation taking place within the skin. Herein, we focus on the key relationships between TNF-α and distinct skin non-neoplastic inflammatory or physiologic conditions, showing that a natural induction of TNF-α may have a protective significance but that TNF-α overproduction may be harmful or even lethal. Many questions remain unraveled in the therapeutic practice, and caution should be exercised due to eventual backlashes exerted by TNF-α in maintaining skin health or in provoking skin disease.
皮肤是肿瘤坏死因子-α（TNF-α）的多种功能的前沿，作为一种促炎细胞因子，TNF-α具有令人瞩目的多功能性和对组织稳态、免疫反应、血管生成、细胞凋亡、局部和全身炎症的重要意义。异常的 TNF-α 介导的串扰与急性和慢性皮肤炎症性疾病的发病机制有关，事实上，TNF-α 失调可能导致银屑病、白癜风、紫外线辐射暴露后的局部损伤、皮肤红斑狼疮和寻常痤疮的发展和进展。针对 TNF-α 的治疗方法在治疗不同的皮肤疾病中得到了广泛应用，旨在调节体内许多皮肤细胞（包括角质形成细胞、肥大细胞或朗格汉斯细胞）触发的免疫功能，并减轻皮肤内发生的炎症。在此，我们重点关注 TNF-α 与不同的非肿瘤性皮肤炎症或生理状况之间的关键关系，表明 TNF-α 的自然诱导可能具有保护意义，但 TNF-α 的过度产生可能是有害的，甚至是致命的。在治疗实践中仍有许多问题尚未解决，由于 TNF-α 在维持皮肤健康或引发皮肤疾病方面可能产生的反弹作用，应谨慎行事。
