Klotz Daniela, Baumgärtner Wolfgang, Gerhauser Ingo
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany; Center of Systems Neuroscience Hannover, Hannover, Germany.
Vet Immunol Immunopathol. 2017 Sep;191:80-93. doi: 10.1016/j.vetimm.2017.08.006. Epub 2017 Aug 26.
Type I interferons (IFNs) such as IFN-α, IFN-β, IFN-ε, IFN-κ, and IFN-ω represent cytokines, which are deeply involved in the regulation and activation of innate and adaptive immune responses. They possess strong antiviral, antiproliferative, and immunomodulatory activities allowing their use in the therapy of different viral diseases, neoplasms, and immune-mediated disorders, respectively. Initially, treatment strategies were based on nonspecific inducers of type I IFNs, which were soon replaced by different recombinant proteins. Drugs with type I IFNs as active agents are currently used in the treatment of hepatitis B and C virus infection, lymphoma, myeloid leukemia, renal carcinoma, malignant melanoma, and multiple sclerosis in humans. In addition, recombinant feline IFN-ω has been approved for the treatment of canine parvovirus, feline leukemia virus, and feline immunodeficiency virus infections. However, the role of type I IFNs in the pathogenesis of canine diseases remains largely undetermined so far, even though some share pathogenic mechanisms and clinical features with their human counterparts. This review summarizes the present knowledge of type I IFNs and down-stream targets such as Mx and 2',5'-oligoadenylate synthetase proteins in the pathogenesis of infectious and immune-mediated canine diseases. Moreover, studies investigating the potential use of type I IFNs in the treatment of canine lymphomas, melanomas, sarcomas, and carcinomas, canine distemper virus, parvovirus, and papillomavirus infections as well as immune-mediated keratoconjunctivitis sicca and atopic dermatitis are presented. A separate chapter is dedicated to the therapeutic potential of IFN-λ, a type III IFN, in canine diseases. However, further future studies are still needed to unravel the exact functions of the different subtypes of type I IFNs and their target genes in healthy and diseased dogs and the full potential action of type I IFNs as treatment strategy.
I型干扰素（IFN），如IFN-α、IFN-β、IFN-ε、IFN-κ和IFN-ω，是一类细胞因子，它们在固有免疫和适应性免疫反应的调节与激活过程中发挥着重要作用。它们具有强大的抗病毒、抗增殖和免疫调节活性，分别可用于治疗不同的病毒性疾病、肿瘤和免疫介导性疾病。最初，治疗策略基于I型干扰素的非特异性诱导剂，但很快就被不同的重组蛋白所取代。目前，以I型干扰素为活性剂的药物被用于治疗人类的乙型和丙型肝炎病毒感染、淋巴瘤、髓系白血病、肾癌、恶性黑色素瘤和多发性硬化症。此外，重组猫干扰素-ω已被批准用于治疗犬细小病毒、猫白血病病毒和猫免疫缺陷病毒感染。然而，尽管犬类疾病与人类疾病在某些致病机制和临床特征上存在相似之处，但I型干扰素在犬类疾病发病机制中的作用至今仍 largely未明。本综述总结了目前关于I型干扰素及其下游靶点（如Mx和2',5'-寡腺苷酸合成酶蛋白）在犬类感染性和免疫介导性疾病发病机制中的认识。此外，还介绍了关于I型干扰素在治疗犬淋巴瘤、黑色素瘤、肉瘤和癌、犬瘟热病毒、细小病毒和乳头瘤病毒感染以及免疫介导的干燥性角结膜炎和特应性皮炎方面潜在用途的研究。单独的一章专门讨论了III型干扰素IFN-λ在犬类疾病中的治疗潜力。然而，仍需要进一步的研究来阐明I型干扰素不同亚型及其靶基因在健康和患病犬中的确切功能，以及I型干扰素作为治疗策略的全部潜在作用。
