Immunosafety evaluation in Juvenile Göttingen Minipigs.

IF 2.4 4区 医学 Q3 TOXICOLOGY Journal of Immunotoxicology Pub Date : 2022-12-01 DOI:10.1080/1547691X.2022.2088904
Linda Allais, Alicia Perbet, Fabienne Condevaux, Jean-Paul Briffaux, Marc Pallardy
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Abstract

Although an extrapolation from the clinical experience in adults can often be considered to support the pediatric use for most pharmaceutical compounds, differences in safety profiles between adult and pediatric patients can be observed. The developing immune system may be affected due to exaggerated pharmacological or non-expected effects of a new drug. Toxicology studies in juvenile animals could therefore be required to better evaluate the safety profile of any new pharmaceutical compound targeting the pediatric population. The Göttingen minipig is now considered a useful non-rodent species for non-clinical safety testing of human pharmaceuticals. However, knowledge on the developing immune system in juvenile minipigs is still limited. The objective of the work reported here was to evaluate across-age proportions of main immune cells circulating in blood or residing in lymphoid organs (thymus, spleen, lymph nodes) in Göttingen Minipigs. In parallel, the main immune cell populations from healthy and immunocompromised piglets were compared following treatment with cyclosporin A (CsA) at 10 mg/kg/day for 4 wk until weaning. The study also assessed functionality of immune responses using an in-vivo model after "Keyhole limpet hemocyanin" (KLH) immunization and an ex-vivo lymph proliferation assay after stimulation with Concanavalin A. The results demonstrated variations across age in circulating immune cell populations including CD21+ B-cells, αβ-T- and γδ-T-cells, NK cells, and monocytes. CsA-induced changes in immune functions were only partially recovered by 5 mo after the end of treatment, whereas the immune cell populations affected by the treatment returned to normal levels in animals of the same age. Taken together, the study here shows that in this model, the immune function endpoints were more sensitive than the immunophenotyping endpoints.

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幼龄Göttingen迷你猪免疫安全性评价。
虽然从成人的临床经验推断,通常可以认为支持儿童使用大多数药物化合物,但可以观察到成人和儿童患者在安全性方面的差异。正在发育的免疫系统可能由于新药的夸张药理作用或非预期作用而受到影响。因此,需要对幼龄动物进行毒理学研究,以更好地评估任何针对儿科人群的新药物化合物的安全性。Göttingen迷你猪现在被认为是一种有用的非啮齿类动物,用于人类药物的非临床安全性测试。然而,关于幼猪免疫系统发育的知识仍然有限。本文报道的工作目的是评估Göttingen迷你猪血液循环或淋巴器官(胸腺、脾脏、淋巴结)中主要免疫细胞的跨年龄比例。同时,对健康仔猪和免疫功能低下仔猪的主要免疫细胞群进行比较,以10 mg/kg/天的剂量给予环孢素A (CsA),持续4周至断奶。该研究还利用“锁眼帽贝血青素”(KLH)免疫后的体内模型和刺豆蛋白a刺激后的体外淋巴增殖试验评估了免疫反应的功能。结果表明,循环免疫细胞群包括CD21+ b细胞、αβ-T细胞和γδ- t细胞、NK细胞和单核细胞在不同年龄之间存在差异。在治疗结束后5个月,csa引起的免疫功能变化仅部分恢复,而在同龄动物中,受治疗影响的免疫细胞群恢复到正常水平。综上所述,本研究表明,在该模型中,免疫功能终点比免疫表型终点更敏感。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Immunotoxicology
Journal of Immunotoxicology 医学-毒理学
CiteScore
6.70
自引率
3.00%
发文量
26
审稿时长
1 months
期刊介绍: The Journal of Immunotoxicology is an open access, peer-reviewed journal that provides a needed singular forum for the international community of immunotoxicologists, immunologists, and toxicologists working in academia, government, consulting, and industry to both publish their original research and be made aware of the research findings of their colleagues in a timely manner. Research from many subdisciplines are presented in the journal, including the areas of molecular, developmental, pulmonary, regulatory, nutritional, mechanistic, wildlife, and environmental immunotoxicology, immunology, and toxicology. Original research articles as well as timely comprehensive reviews are published.
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