Kentner A C, Miguelez M, James J S, Bielajew C
School of Psychology, University of Ottawa, 11 Marie Curie, Room 108, Ottawa, Canada K1N 6N5.
Brain Res. 2006 Jun 20;1095(1):96-106. doi: 10.1016/j.brainres.2006.04.014. Epub 2006 May 18.
Interferon-alpha (IFN-alpha) is a cytokine used as a first line of defense against diseases such as cancer and hepatitis C. However, reports indicate that its effectiveness as a treatment is countered by central nervous system (CNS) disruptions in patients. Our work explored the possibility that it may also cause long-term behavioral disruptions by chronicling the behavioral and physiological disturbances associated with a single injection of vehicle, 10, 100, or 1,000 units of IFN-alpha in male Sprague-Dawley rats (n = 5/dose). Following 1 day of locomotor baseline collection, we monitored sickness behaviors (ptosis, piloerection, lethargy, and sleep), food and water intake, body weight, temperature, and motor activity. Observations were recorded 4 days prior to and 4 days following the IFN-alpha injection. Temperature and sickness behaviors were recorded three times daily at 9:00, 15:00, and 21:00 h, and all other indices, once daily. On the injection day, temperature values were highest in the animals receiving the 10-unit IFN-alpha dose 15 min and 13 h post-injection. In the case of sickness behaviors, a significant increase was observed in piloerection in all IFN-alpha groups at each time point measured, while the scores of the rats in the vehicle condition remained unchanged between pre- and post-injection days. Analyses of overall sickness behaviors during morning and night observation periods indicated increased scores in all IFN-alpha groups following injection. Cumulatively, these data suggest that a single IFN-alpha exposure may elicit long-term behavioral disruptions and that its consequences should be thoroughly investigated for its use in clinical populations.
干扰素-α(IFN-α)是一种细胞因子,用作对抗癌症和丙型肝炎等疾病的第一道防线。然而,报告显示,患者的中枢神经系统(CNS)紊乱会抵消其作为治疗手段的有效性。我们的研究通过记录雄性斯普拉格-道利大鼠(每组n = 5)单次注射赋形剂、10、100或1000单位IFN-α后出现的行为和生理紊乱,探究了它是否也可能导致长期行为紊乱。在收集1天的运动基线后,我们监测了疾病行为(眼睑下垂、竖毛、嗜睡和睡眠)、食物和水摄入量、体重、体温以及运动活动。在IFN-α注射前4天和注射后4天进行观察记录。体温和疾病行为在每天的9:00、15:00和21:00记录三次,其他所有指标每天记录一次。在注射当天,接受10单位IFN-α剂量的动物在注射后15分钟和13小时体温值最高。就疾病行为而言,在每个测量时间点,所有IFN-α组的竖毛行为均显著增加,而赋形剂组大鼠在注射前后的得分保持不变。对早晚观察期内总体疾病行为的分析表明,注射后所有IFN-α组的得分均增加。总体而言,这些数据表明,单次接触IFN-α可能引发长期行为紊乱,其后果在临床应用中应进行深入研究。