Orsal Arif S, Blois Sandra M, Bermpohl Daniela, Schaefer Martin, Coquery Nicolas
Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitatsmedizin Berlin, Campus Mitte, Berlin, Germany.
Neuropsychobiology. 2008;58(3-4):211-22. doi: 10.1159/000201718. Epub 2009 Feb 12.
Interferon-alpha (IFN-alpha) is used in the treatment of many viral and malignant diseases. Although IFN-alpha administration is highly efficacious, treatment is often complicated by psychiatric side effects such as depression, which may require discontinuation of the therapy. Unfortunately, the mechanisms underlying IFN-alpha-induced depression are still not well understood.
In this study, we explored behavioral and immune effects of IFN-alpha administration in mice. BALB/c mice received daily intraperitoneal injections of 60,000 U/kg murine IFN-alpha for 8 days. Behavioral and immunological analysis was performed at least 15 h after injection to avoid any acute IFN-alpha effect. We monitored depression and anxiety-like behavior in mice using the Forced Swimming Test (FST), Tail Suspension Test (TST), and Elevated Plus Maze (EPM). Moreover, we studied the expression of adhesion molecules on peripheral blood leukocytes and analyzed the recruitment of lymphocyte subsets into the brain.
IFN-alpha administration resulted in increased immobility of mice in the late phase of FST, without significant effects in TST and EPM. Increased percentages of natural killer cells and lymphocytes expressing LFA-1 or Mac-1 were observed in peripheral blood. The percentages of CD4+ and CD8+ lymphocytes as well as the percentages of LFA-1-expressing CD4+ and CD8+ lymphocytes were increased in the brains of IFN-alpha-treated mice.
Our data suggest that IFN-alpha administration leads to an increase in peripheral blood cells with migratory potential, accompanied by an increased number of lymphocytes in brain, whilst the detectable modulation of the behavior was rather modest.
α干扰素（IFN-α）用于治疗多种病毒和恶性疾病。尽管IFN-α给药具有高效性，但治疗常因抑郁等精神副作用而变得复杂，这可能需要停止治疗。不幸的是，IFN-α诱导抑郁的潜在机制仍未得到充分理解。
在本研究中，我们探讨了IFN-α给药对小鼠行为和免疫的影响。BALB/c小鼠每天腹腔注射60,000 U/kg小鼠IFN-α，持续8天。在注射后至少15小时进行行为和免疫学分析，以避免任何急性IFN-α效应。我们使用强迫游泳试验（FST）、悬尾试验（TST）和高架十字迷宫（EPM）监测小鼠的抑郁和焦虑样行为。此外，我们研究了外周血白细胞上黏附分子的表达，并分析了淋巴细胞亚群向脑内的募集情况。
IFN-α给药导致FST后期小鼠不动时间增加，而在TST和EPM中无显著影响。在外周血中观察到表达LFA-1或Mac-1的自然杀伤细胞和淋巴细胞百分比增加。在IFN-α处理小鼠的脑中，CD4+和CD8+淋巴细胞百分比以及表达LFA-1的CD4+和CD8+淋巴细胞百分比增加。
我们的数据表明，IFN-α给药导致具有迁移潜力的外周血细胞增加，同时脑内淋巴细胞数量增加，而行为的可检测调节较为适度。
