Effect of the ketone beta-hydroxybutyrate on markers of inflammation and immune function in adults with type 2 diabetes.

IF 3.4 3区 医学 Q3 IMMUNOLOGY
Helena Neudorf, Hashim Islam, Kaja Falkenhain, Barbara Oliveira, Garett S Jackson, Alfonso Moreno-Cabañas, Kenneth Madden, Joel Singer, Jeremy J Walsh, Jonathan P Little
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Abstract

Pre-clinical and cell culture evidence supports the role of the ketone beta-hydroxybutyrate (BHB) as an immunomodulatory molecule that may inhibit inflammatory signalling involved in several chronic diseases such as type 2 diabetes (T2D), but studies in humans are lacking. Therefore, we investigated the anti-inflammatory effect of BHB in humans across three clinical trials. To investigate if BHB suppressed pro-inflammatory cytokine secretion, we treated LPS-stimulated leukocytes from overnight-fasted adults at risk for T2D with BHB (Study 1). Next (Study 2), we investigated if exogenously raising BHB acutely in vivo by ketone monoester supplementation (KME) in adults with T2D would suppress pro-inflammatory plasma cytokines. In Study 3, we investigated the effect of BHB on inflammation via ex vivo treatment of LPS-stimulated leukocytes with BHB and in vivo thrice-daily pre-meal KME for 14 days in adults with T2D. Ex vivo treatment with BHB suppressed LPS-stimulated IL-1β, TNF-α, and IL-6 secretion and increased IL-1RA and IL-10 (Study 1). Plasma IL-10 increased by 90 min following ingestion of a single dose of KME in T2D, which corresponded to peak blood BHB (Study 2). Finally, 14 days of thrice-daily KME ingestion did not significantly alter plasma cytokines or leukocyte subsets including monocyte and T-cell polarization (Study 3). However, direct treatment of leukocytes with BHB modulated TNF-α, IL-1β, IFN-γ, and MCP-1 secretion in a time- and glucose-dependent manner (Study 3). Therefore, BHB appears to be anti-inflammatory in T2D, but this effect is transient and is modulated by the presence of disease, glycaemia, and exposure time.

酮体β-羟丁酸对 2 型糖尿病成人炎症和免疫功能指标的影响。
临床前和细胞培养的证据支持酮体 beta-羟丁酸(BHB)作为一种免疫调节分子的作用,它可以抑制 2 型糖尿病(T2D)等多种慢性疾病所涉及的炎症信号传导,但缺乏对人体的研究。因此,我们通过三项临床试验研究了 BHB 在人体中的抗炎作用。为了研究 BHB 是否能抑制促炎细胞因子的分泌,我们用 BHB 处理了隔夜禁食的有 T2D 风险的成人的 LPS 刺激白细胞(研究 1)。接下来(研究 2),我们研究了通过补充酮一酯(KME)在体内急性提高 BHB 是否会抑制 T2D 成人的促炎性血浆细胞因子。在研究 3 中,我们用 BHB 对 LPS 刺激的白细胞进行体外处理,并在 T2D 患者体内连续 14 天每天三次在餐前补充 KME,从而研究了 BHB 对炎症的影响。BHB体内外治疗可抑制LPS刺激的IL-1β、TNF-α和IL-6的分泌,并增加IL-1RA和IL-10(研究1)。在 T2D 患者摄入单剂量 KME 90 分钟后,血浆 IL-10 增高,这与血液中 BHB 的峰值相对应(研究 2)。最后,14 天内每天三次摄入 KME 不会显著改变血浆细胞因子或白细胞亚群,包括单核细胞和 T 细胞极化(研究 3)。然而,用 BHB 直接处理白细胞可调节 TNF-α、IL-1β、IFN-γ 和 MCP-1 的分泌,调节方式与时间和葡萄糖有关(研究 3)。因此,BHB 似乎对 T2D 有抗炎作用,但这种作用是短暂的,并受疾病、血糖和暴露时间的影响。
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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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