Frank M G, Hendricks S E, Johnson D R, Wieseler J L, Burke W J
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebr., USA.
Neuropsychobiology. 1999;39(1):18-24. doi: 10.1159/000026555.
Depressed mood has been associated with reduced natural killer cell activity (NKCA). Further, amelioration of depressive symptoms by pharmacotherapy has resulted in augmented NKCA. Serotonin, an indoleamine implicated in the pathophysiology of affective disorders, enhances NKCA in vitro and lymphocytes possess serotonin transporters and receptors. The present study evaluated NKCA in depressed outpatients before and during treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac(R)). Further, the SSRIs, fluoxetine and paroxetine (Paxil(R)), were also incubated in vitro with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA. Depressed outpatients were administered fluoxetine (20 mg/day) for 4 weeks. NKCA and severity of depression were evaluated at weeks 0, 1, 2, and 4. Serum concentrations of fluoxetine and norfluoxetine were obtained as well. Mononuclear cells obtained from nonpatient volunteers were incubated with pharmacologic concentrations of fluoxetine or paroxetine and NKCA measured with a standard chromium release assay. Fluoxetine treatment resulted in decreased symptoms of depression and increased serum concentrations of fluoxetine and norfluoxetine. Further, fluoxetine treatment was associated with augmented NKCA in a subgroup of depressed outpatients exhibiting low NKCA at baseline. Fluoxetine had no effect on NKCA in depressed individuals exhibiting high NKCA at baseline. Incubation of mononuclear cells with fluoxetine and paroxetine augmented NKCA in vitro. The enhancing effects of antidepressants on NKCA in vivo and in vitro indicate a possible direct drug interaction with lymphoid cells during pharmacotherapy, suggesting that pharmacologic treatment of depression may result in enhanced immune competence as indexed by enhanced NKCA and that NKCA could be pharmacologically augmented with antidepressants in individuals with compromised immune function.
情绪低落与自然杀伤细胞活性（NKCA）降低有关。此外，药物治疗改善抑郁症状后，NKCA会增强。血清素是一种与情感障碍病理生理学有关的吲哚胺，它在体外可增强NKCA，且淋巴细胞拥有血清素转运体和受体。本研究评估了在使用选择性血清素再摄取抑制剂（SSRI）氟西汀（百忧解®）治疗前及治疗期间，门诊抑郁症患者的NKCA。此外，还将SSRI类药物氟西汀和帕罗西汀（帕罗西汀®）与淋巴细胞进行体外孵育，以评估SSRI对NKCA可能的直接作用。门诊抑郁症患者服用氟西汀（20毫克/天），持续4周。在第0、1、2和4周评估NKCA和抑郁严重程度。同时获取氟西汀和去甲氟西汀的血清浓度。从非患者志愿者获取的单核细胞与药理浓度的氟西汀或帕罗西汀孵育，并用标准铬释放试验测量NKCA。氟西汀治疗导致抑郁症状减轻，氟西汀和去甲氟西汀的血清浓度升高。此外，在基线时NKCA较低的一组门诊抑郁症患者中，氟西汀治疗与NKCA增强有关。氟西汀对基线时NKCA较高的抑郁症患者的NKCA没有影响。单核细胞与氟西汀和帕罗西汀体外孵育可增强NKCA。抗抑郁药在体内和体外对NKCA的增强作用表明，在药物治疗期间可能存在与淋巴细胞的直接药物相互作用，这表明抑郁症的药物治疗可能导致以NKCA增强为指标的免疫能力增强，并且在免疫功能受损的个体中，抗抑郁药可在药理学上增强NKCA。
