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标题：Growth differentiation factor 15 neutralization does not impact anorexia or survival in lipopolysaccharide-induced inflammation
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作者：Danna M. Breen ; Srinath Jagarlapudi ; Anita Patel 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：6
页码：1-20
DOI：10.1016/j.isci.2021.102554
语种：English
出版社：Elsevier
摘要：SummaryGrowth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, and higher circulating levels are associated with cachexia and reduced survival in cancer and other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated and highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, weight loss, and mortality in rodents. LPS injection transiently increased circulating GDF15 in wild-type mice, decreased food intake and body weight, and increased illness behavior and mortality at a high dose. GDF15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. Similarly, in GDF15 knockout mice, the LPS effect on appetite and survival was comparable with that observed in wild-type controls. Therefore, effective inhibition of circulating active GDF15 via an antibody or via gene knockout demonstrated that survival in the LPS acute inflammation model was independent of GDF15.Graphical abstractDisplay OmittedHighlights•A novel highly potent anti-GDF15 antibody, mAB2, was characterized•LPS transiently increased GDF15 production in mice•mAB2 did not prevent or exacerbate the effects of LPS on anorexia or survival•GDF15 knockout mice showed comparable effects of LPS with wild-type controlsCell biology; Physiology;