Schaefer Martin, Horn Martin, Schmidt Folkhard, Schmid-Wendtner Monika H, Volkenandt Matthias, Ackenheil Manfred, Mueller Norbert, Schwarz Markus J
Department of Psychiatry, Charité-University Medicine Berlin, Campus Charité Mitte, Schumannstr. 20/21, D-10117 Berlin, Germany.
Brain Behav Immun. 2004 Nov;18(6):555-62. doi: 10.1016/j.bbi.2004.02.002.
Interferon-alpha (IFN-alpha) treatment is frequently complicated by symptoms of depression. The mechanism by which peripherally administered IFN-alpha enters and modulates the central nervous system remains unclear. The cell adhesion molecule ICAM-1 is involved in the regulation of blood-brain barrier (BBB) permeability. ICAM-1 expression was shown to increase during IFN-alpha treatment and recently the expression of ICAM-1 on vascular endothelial cells in the brain was found to be correlated with the development of depression. We therefore hypothesized that soluble ICAM-1 may be involved in the development of IFN-alpha associated depression. In a prospective study, serum levels of soluble ICAM-1 (double sandwich ELISA test) and symptoms of depression (SDS) were measured in 48 patients with malignant melanoma before and during adjuvant IFN-alpha treatment. Both, depression scores and the serum levels of sICAM-1 significantly increased after three months of IFN-alpha treatment compared to baseline levels (p < .001). Patients who developed depression (SDS-index scores > or = 50) after three months of treatment had higher sICAM-1 levels compared to non-depressed patients. Furthermore, sICAM-1 levels were positively correlated with SDS values (r = .367, p = .018). Our data provides evidence for an association between the induction of sICAM-1 and the development of symptoms of depression during IFN-alpha treatment, possibly by enhancing BBB-permeability.
α-干扰素(IFN-α)治疗常常伴有抑郁症状。外周给予的IFN-α进入并调节中枢神经系统的机制尚不清楚。细胞黏附分子ICAM-1参与血脑屏障(BBB)通透性的调节。研究表明,在IFN-α治疗期间ICAM-1表达增加,最近发现大脑血管内皮细胞上ICAM-1的表达与抑郁症的发生有关。因此,我们推测可溶性ICAM-1可能与IFN-α相关抑郁症的发生有关。在一项前瞻性研究中,对48例恶性黑色素瘤患者在辅助IFN-α治疗前及治疗期间测定了可溶性ICAM-1的血清水平(双夹心ELISA检测)和抑郁症状(SDS)。与基线水平相比,IFN-α治疗三个月后,抑郁评分和sICAM-1血清水平均显著升高(p <.001)。治疗三个月后出现抑郁的患者(SDS指数评分>或=50)与未抑郁患者相比,sICAM-1水平更高。此外,sICAM-1水平与SDS值呈正相关(r =.367,p =.018)。我们的数据为IFN-α治疗期间sICAM-1的诱导与抑郁症状的发生之间的关联提供了证据,可能是通过增强血脑屏障通透性实现的。