Department of Psychology, University of California at Los Angeles, Los Angeles, California, USA.
Neuroscience Interdepartmental Program, University of California at Los Angeles, Los Angeles, California, USA.
Addict Biol. 2022 Jul;27(4):e13182. doi: 10.1111/adb.13182.
Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro-inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and potential central markers of inflammation in individuals with AUD. This study also explored the predictive relationship of neurometabolite markers with subsequent drinking in the trial. Non-treatment-seeking individuals with an AUD (n = 52) were randomized to receive oral ibudilast (n = 24) or placebo (n = 28) for 2 weeks. Plasma levels of peripheral inflammatory markers were measured at baseline and after 1 and 2 weeks of medication. At study mid-point, proton magnetic resonance spectroscopy was performed to measure potential neurometabolite markers of inflammation: choline-compounds (Cho), myo-inositol (MI) and creatine + phosphocreatine (Cr) in frontal and cingulate cortices from 43 participants (ibudilast: n = 20; placebo: n = 23). The treatment groups were compared on peripheral and central markers. Ibudilast-treated participants had lower Cho in superior frontal white matter and nominally lower MI in pregenual anterior cingulate cortex. Ibudilast-treated participants had nominally lower C-reactive protein levels at visit 2 and nominally lower TNF-α/IL-10 ratios, relative to placebo. C-reactive protein and Cho levels were correlated, controlling for medication. Superior frontal white matter Cho predicted drinking in the following week. Micro-longitudinal ibudilast treatment may induce peripheral and putative central anti-inflammatory responses in patients with AUD. The neurometabolite responses may be associated with reduction in drinking, suggesting an anti-inflammatory component to the therapeutic action of ibudilast.
伊布地尔是一种神经免疫调节剂，有望成为治疗酒精使用障碍（AUD）的药物。在动物模型中，伊布地尔的体内给药可降低促炎细胞因子的表达，但它对人类炎症标志物的影响尚不清楚。本初步研究探讨了伊布地尔对 AUD 患者外周和潜在中枢炎症标志物的影响。本研究还探讨了试验中神经代谢物标志物与随后饮酒之间的预测关系。非治疗寻求的 AUD 个体（n=52）随机分为口服伊布地尔（n=24）或安慰剂（n=28）组，疗程为 2 周。在基线、用药 1 周和 2 周时测量外周炎症标志物的血浆水平。在研究中点，进行质子磁共振波谱检查以测量潜在的炎症性神经代谢物标志物：胆碱化合物（Cho）、肌醇（MI）和额皮质和扣带回皮质中的肌酸+磷酸肌酸（Cr）来自 43 名参与者（伊布地尔：n=20；安慰剂：n=23）。比较了治疗组的外周和中枢标志物。伊布地尔治疗组参与者的额上白质中的 Cho 降低，前扣带回皮质的前扣带前皮质中的 MI 降低。与安慰剂相比，伊布地尔治疗组参与者在第 2 次就诊时的 C 反应蛋白水平降低，TNF-α/IL-10 比值降低。控制药物后，C 反应蛋白和 Cho 水平相关。额上白质 Cho 预测下周饮酒。微纵向伊布地尔治疗可能会诱导 AUD 患者的外周和潜在中枢抗炎反应。神经代谢物反应可能与饮酒减少有关，表明伊布地尔的治疗作用具有抗炎成分。
