Linda Allais, Alicia Perbet, Fabienne Condevaux, Jean-Paul Briffaux, Marc Pallardy
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引用次数: 0
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.
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.