期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 25, 期 6, 页码 1094-1098出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2011.02.015
关键词
Interferon-alpha; p38 Mitogen activated protein kinase; Cytokines; Depression; Fatigue; Flow cytometry; Cortisol; Innate immunity
资金
- National Institutes of Health [K23 MH064619, R01 MH070553, K05 MH069124, R01 HL073921, MHR01MH075102, T32 MH020018]
- Emory Center for AIDS Research [P30 AI050409]
- Flow Cytometry Core Facility of the Emory University School of Medicine
- PHS [UL1 RR025008, M01 RR0039]
- National Institutes of Health, National Center for Research Resources
Cytokine-induced stimulation of p38 mitogen activated protein kinase (MAPK) has been shown to influence behaviorally-relevant pathophysiologic pathways including monoamine neurotransmission and neuroendocrine function and thus may contribute to behavioral changes that occur during chronic administration of the innate immune cytokine, interferon (IFN)-alpha. Accordingly, in the current study, phosphorylation (activation) of intracellular p38 MAPK in peripheral blood lymphocytes was analyzed by flow cytometry every 2 h for 12 h following the initial injection of IFN-alpha in eleven patients with chronic hepatitis C. Hourly assessments of plasma concentrations of adrenocorticotropic hormone, cortisol and interleukin-6 were also obtained. Symptoms of depression and fatigue were measured at baseline and after 4 and 12 weeks of IFN-alpha treatment. Acute administration of IFN-alpha significantly increased the percentage of lymphocytes staining positive for intracellular phosphorylated p38 (p-p38). IFN-alpha-induced increases in p-p38 were significantly greater in patients that developed clinically significant depressive symptoms [Montgomery-Asberg Depression Rating Scale (MADRS) score >= 15]during the first 12 weeks of IFN-alpha treatment. Increases in the percentage of p-p38-positive lymphocytes following the first IFN-alpha injection also highly correlated with depression severity at weeks 4 (r = 0.85, p = 0.001) and 12 (r = 0.70, p = 0.018). Similar relationships were observed for fatigue. Examination of relationships between p-p38 induction and factors previously reported to predict IFN-alpha-induced depressive symptoms revealed strong associations of p-p38 with baseline MADRS (r = 0.82, p = 0.002) and cortisol responses to the initial injection of IFN-alpha (r = 0.91, p = 0.000). Taken together, these findings indicate that sensitivity of p38 MAPK signaling pathways to immune stimulation is associated with depressive symptoms during chronic IFN-alpha treatment. (C) 2011 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据