Professor Emeritus of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street S.W., Rochester, MN, 55905, USA.
Dig Dis Sci. 2022 Apr;67(4):1163-1186. doi: 10.1007/s10620-021-06968-6. Epub 2021 Apr 9.
Transforming growth factor-beta and interleukin 10 have diverse immune inhibitory properties that have restored homeostatic defense mechanisms in experimental models of autoimmune disease. The goals of this review are to describe the actions of each cytokine, review their investigational use in animal models and patients, and indicate their prospects as interventions in autoimmune hepatitis. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Transforming growth factor-beta expands the natural and inducible populations of regulatory T cells, limits the proliferation of natural killer cells, suppresses the activation of naïve CD8 T cells, decreases the production of interferon-gamma, and stimulates fibrotic repair. Interleukin 10 selectively inhibits the CD28 co-stimulatory signal for antigen recognition and impairs antigen-specific activation of uncommitted CD4 and CD8 T cells. It also inhibits maturation of dendritic cells, suppresses Th17 cells, supports regulatory T cells, and limits production of diverse pro-inflammatory cytokines. Contradictory immune stimulatory effects have been associated with each cytokine and may relate to the dose and accompanying cytokine milieu. Experimental findings have not translated into successful early clinical trials. The recombinant preparation of each agent in low dosage has been safe in human studies. In conclusion, transforming growth factor-beta and interleukin 10 have powerful immune inhibitory actions of potential therapeutic value in autoimmune hepatitis. The keys to their therapeutic application will be to match their predominant non-redundant function with the pivotal pathogenic mechanism or cytokine deficiency and to avoid contradictory immune stimulatory actions.
转化生长因子-β和白细胞介素 10 具有多种免疫抑制特性，可在自身免疫性疾病的实验模型中恢复体内稳态防御机制。本综述的目的是描述每种细胞因子的作用，回顾其在动物模型和患者中的研究应用，并指出它们作为自身免疫性肝炎干预措施的前景。通过多个搜索词在 PubMed 中确定英文摘要。选择全文进行综述，并进一步发展二级和三级参考文献。转化生长因子-β可扩增自然和诱导型调节性 T 细胞群体，限制自然杀伤细胞的增殖，抑制幼稚 CD8 T 细胞的激活，减少干扰素-γ的产生，并刺激纤维化修复。白细胞介素 10 选择性抑制 CD28 共刺激信号以识别抗原，并损害未定型 CD4 和 CD8 T 细胞的抗原特异性激活。它还抑制树突状细胞的成熟，抑制 Th17 细胞，支持调节性 T 细胞，并限制多种促炎细胞因子的产生。每种细胞因子都与矛盾的免疫刺激作用相关，这可能与剂量和伴随的细胞因子环境有关。实验结果并未转化为成功的早期临床试验。在人类研究中，每种药物的低剂量重组制剂是安全的。总之，转化生长因子-β和白细胞介素 10 具有强大的免疫抑制作用，在自身免疫性肝炎中具有潜在的治疗价值。治疗应用的关键将是将其主要的非冗余功能与关键的致病机制或细胞因子缺乏相匹配，并避免矛盾的免疫刺激作用。
