Depression is associated with peripheral inflammation, but its link with brain microglial activity remains unclear. In seven healthy males, we used repeated translocator protein-Positron Emission Tomography (TSPO-PET) dynamic scans with [¹¹C]PBR28 to image brain microglial activation before and 24 h after the immune challenge interferon (IFN)-α. We also investigated the association between changes in peripheral inflammation, changes in microglial activity, and changes in mood. IFN-α administration decreased [¹¹C]PBR28 PET tissue volume of distribution (Vt) across the brain (−20 ± 4%; t₆ = 4.1, p = 0.01), but after correction for radioligand free-plasma fraction there were no longer any changes (+23 ± 31%; t = 0.1, p = 0.91). IFN-α increased serum IL-6 (1826 ± 513%, t₆ = −7.5, p < 0.001), IL-7 (39 ± 12%, t₆ = −3.6, p = 0.01), IL-10 (328 ± 48%, t₆ = −12.8, p < 0.001), and IFN-γ (272 ± 64%, t₆ = −7.0, p < 0.001) at 4–6 h, and increased serum TNF-α (49 ± 7.6%, t₆ = −7.5, p < 0.001), IL-8 (39 ± 12%, t₆ = −3.5, p = 0.013), and C-reactive protein (1320 ± 459%, t₆ = −7.2, p < 0.001) at 24 h. IFN-α induced temporary mood changes and sickness symptoms after 4–6 h, measured as an increase in POMS-2 total mood score, confusion and fatigue, and a decrease in vigor and friendliness (all p ≤ 0.04). No association was found between changes in peripheral inflammation and changes in PET or mood measures. Our work suggests that brain TSPO-PET signal is highly dependent of inflammation-induced changes in ligand binding to plasma proteins. This limits its usefulness as a sensitive marker of neuroinflammation and consequently, data interpretation. Thus, our results can be interpreted as showing either that [¹¹C]PBR28 is not sensitive enough under these conditions, or that there is simply no microglial activation in this model.

抑郁症与周围炎症有关，但其与大脑小胶质细胞活动的关系仍不清楚。在七名健康男性中，我们使用[ ¹¹ C]PBR28重复易位蛋白正电子发射断层扫描（TSPO-PET）动态扫描，对免疫攻击干扰素（IFN）-α之前和之后24小时的脑小胶质细胞激活进行成像。我们还研究了外周炎症变化、小胶质细胞活性变化和情绪变化之间的关联。 IFN-α给药降低了[ ¹¹ C]PBR28 PET组织分布体积（Vt）在大脑中的分布（−20 ± 4%；t ₆ = 4.1， p = 0.01），但在校正放射性配体游离血浆分数后，没有出现任何变化的时间更长（+23 ± 31%；t = 0.1， p = 0.91）。 IFN-α 增加血清 IL-6 (1826 ± 513%, t ₆ = -7.5, p < 0.001)、IL-7 (39 ± 12%, t ₆ = -3.6, p = 0.01)、IL-10 ( 328 ± 48%，t ₆ = -12.8， p < 0.001)，4-6 小时时 IFN-γ (272 ± 64%，t ₆ = -7.0， p < 0.001)，血清 TNF-α 增加(49 ± 7.6%, t ₆ = −7.5, p < 0.001)、IL-8 (39 ± 12%, t ₆ = −3.5, p = 0.013) 和 C 反应蛋白 (1320 ± 459%, t ₆ = -7.2, p < 0.001) 在 24 小时。 IFN-α 在 4-6 小时后引起暂时的情绪变化和疾病症状，测量为 POMS-2 总情绪评分、困惑和疲劳的增加，以及活力和友善度的下降（​​所有p ≤ 0.04）。未发现外周炎症的变化与 PET 或情绪测量的变化之间存在关联。 我们的工作表明，大脑 TSPO-PET 信号高度依赖于炎症诱导的配体与血浆蛋白结合的变化。这限制了它作为神经炎症敏感标记的有用性，从而限制了数据解释。因此，我们的结果可以解释为表明[ ¹¹ C]PBR28 在这些条件下不够敏感，或者该模型中根本没有小胶质细胞激活。