Targeting inflammation to influence mood following spinal cord injury: a randomized clinical trial

Background: The purpose of the present study was to examine the efficacy of targeting inflammation as a means of improving mood following spinal cord injury (SCI) and explore the potential mechanisms of action.Methods: The study was a randomized, parallel-group, controlled, clinical trial (NCT02099890) whereby 20 participants with varying levels and severities of SCI were randomized (3:2) to either the treatment group, consisting of a 12-week anti-inflammatory diet, or control group. Outcome measures were assessed at baseline, 1 and 3 months, and consisted of CES-D scores of depression, markers of inflammation as assessed by various pro-and anti-inflammatory cytokines and several amino acids related to depression.Results: A significant group x time interaction was found for CES-D (Center for Epidemiologic studies Depression Scale) score (p = 0.01), the TRP/LNAA (tryptophan/large neutral amino acid) ratio (p = 0.04), the composite score of pro-inflammatory cytokines (p = 0.04), IL-1 beta (interleukin-1 beta) (p = 0.04), and IFN-gamma (interferon gamma) (p = 0.03). Pearson's r correlation showed significance between the Delta IL-1 beta and both the Delta CES-D score (r = 0.740, p < 0.01) and the Delta KYN/TRP (kynurenine/tryptophan) ratio (r = 0.536, p = 0.02). The Delta KYN/TRP ratio was also significantly correlated with the Delta CES-D score (r = 0.586, p = 0.01). Mediation analysis showed that the relationship between the Delta KYN/TRP ratio and the Delta CES-D score was mediated by the Delta IL-1 beta. Subgroup analysis showed that participants with high CES-D scores had significantly higher concentrations of IL-1 beta, and all correlations were maintained or strengthened within this subgroup.Conclusions: Overall, the results demonstrated the effectiveness of targeting inflammation as a means of improving mood in SCI, with potential mechanisms relating to the reduction in IL-1 beta and improvements in levels of neuroactive compounds related to the kynurenine pathway. Due to the limited sample size, results should be interpreted with caution; however, they are worthy of further examination due to the potential impact of inflammation on depression.

背景：本研究旨在检验将炎症作为改善脊髓损伤（SCI）后情绪的一种手段的有效性，并探索其潜在作用机制。 方法：该研究是一项随机、平行组、对照临床试验（NCT02099890），20名不同程度和严重程度的脊髓损伤参与者按3∶2的比例随机分配到治疗组（接受为期12周的抗炎饮食）或对照组。在基线、1个月和3个月时评估结果指标，包括抑郁的流调中心用抑郁量表（CES - D）评分、通过各种促炎和抗炎细胞因子评估的炎症标志物以及几种与抑郁相关的氨基酸。 结果：发现流调中心用抑郁量表评分（p = 0.01）、色氨酸/大分子中性氨基酸（TRP/LNAA）比值（p = 0.04）、促炎细胞因子综合评分（p = 0.04）、白细胞介素 - 1β（IL - 1β）（p = 0.04）和干扰素 - γ（IFN - γ）（p = 0.03）存在显著的组×时间交互作用。皮尔逊相关系数显示，ΔIL - 1β与ΔCES - D评分（r = 0.740，p < 0.01）以及Δ犬尿氨酸/色氨酸（KYN/TRP）比值（r = 0.536，p = 0.02）之间具有显著相关性。ΔKYN/TRP比值也与ΔCES - D评分显著相关（r = 0.586，p = 0.01）。中介分析表明，ΔKYN/TRP比值与ΔCES - D评分之间的关系由ΔIL - 1β介导。亚组分析显示，CES - D评分高的参与者IL - 1β浓度显著更高，且在该亚组内所有相关性均保持或增强。 结论：总体而言，结果证明了将炎症作为改善脊髓损伤患者情绪的一种手段是有效的，潜在机制与白细胞介素 - 1β的降低以及犬尿氨酸途径相关的神经活性化合物水平的改善有关。由于样本量有限，对结果应谨慎解读；然而，鉴于炎症对抑郁的潜在影响，这些结果值得进一步研究。