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. 2020 Dec 10;10:21629. doi: 10.1038/s41598-020-78410-2

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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BHB reduces SPS-induced increase in serum inflammatory cytokine levels. (a) Serum TNF-α levels are shown (median [IQR]; non-SPS + Veh: 13.7 [12.4–14.4], SPS + Veh: 20.5 [16.8–20.9], SPS + BHB: 16.1 [15.4–17.2], Kruskal–Wallis test; X2 = 17.265, df = 2, p = 0.0002). SPS exposure increased levels of TNF-α in the blood (Mann–Whitney’s U-test; W = 11, p = 0.001). Chronic BHB treatment decreased levels of TNF-α in the blood in SPS-induced PTSD rats (Mann–Whitney’s U-test; W = 69, p = 0.039). (b) Serum IL-1β levels are shown (median [IQR]; non-SPS + Veh: 28.5 [23.5–31.8], SPS + Veh: 37.1 [33.9–54.3], SPS + BHB: 33.4 [29.7–34.5], Kruskal–Wallis test; X2 = 7.503, df = 2, p = 0.024). SPS increased levels of blood IL-1β (Mann–Whitney’s U-test; W = 34, p = 0.042). Chronic BHB treatment did not significantly decreased levels of IL-1β in the blood of rats exposed to SPS (Mann–Whitney’s U-test; W = 49.5, p = 0.33). The data are presented as scatter plots with median and interquartile range. Kruskal–Wallis test and Mann–Whitney U tests were performed to compare each group. p-values were corrected by Bonferroni method. TNF-α: Tumor necrosis factor-alpha, IL-1β: Interleukin-1 beta, SPS: single prolonged stress, Veh: Vehicle (PBS), BHB: beta-hydroxybutyrate, n = 18 (non SPS + Veh group) or 9 (SPS + Veh group and SPS + BHB group).