- 作者：Charles L. Raison ; Andrey S. Borisov ; Matthias Majer ; Daniel F. Drake ; Giuseppe Pagnoni ; Bobbi J. Woolwine ; Gerald J. Vogt ; Breanne Massung ; Andrew H. Miller
- 关键词：Cerebrospinal fluid ; cytokines ; depression ; inflammation ; monoamines
- 刊名：Biological Psychiatry
- 出版年：2009
- 出版时间：15 February 2009
- 年：2009
- 卷：65
- 期：4
- 页码：296-303
- 全文大小：342 K
Background
Interferon (IFN)-alpha has been used to study the effects of innate immune cytokines on the brain and behavior in humans. The degree to which peripheral administration of IFN-alpha accesses the brain and is associated with a central nervous system (CNS) inflammatory response is unknown. Moreover, the relationship among IFN-alpha-associated CNS inflammatory responses, neurotransmitter metabolism, and behavior has yet to be established.Methods
Twenty-four patients with hepatitis C underwent lumbar puncture and blood sampling after 12 weeks of either no treatment (n = 12) or treatment with pegylated IFN-alpha 2b (n = 12). Cerebrospinal fluid (CSF) and blood samples were analyzed for proinflammatory cytokines and their receptors as well as the chemokine, monocyte chemoattractant protein-1 (MCP-1), and IFN-alpha. Cerebrospinal fluid samples were additionally analyzed for monoamine metabolites and corticotropin releasing hormone. Depressive symptoms were assessed using the Montgomery Asberg Depression Rating Scale.
Results
Interferon-alpha was detected in the CSF of all IFN-alpha-treated patients and only one control subject. Despite no increases in plasma IL-6, IFN-alpha-treated patients exhibited significant elevations in CSF IL-6 and MCP-1, both of which were highly correlated with CSF IFN-alpha concentrations. Of the immunologic and neurotransmitter variables, log-transformed CSF concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were the strongest predictor of depressive symptoms. Log-transformed CSF concentrations of IL-6, but not IFN-alpha or MCP-1, were negatively correlated with log-transformed CSF 5-HIAA (r2 = −.25, p < .05).
Conclusions
These data indicate that a peripherally administered cytokine can activate a CNS inflammatory response in humans that interacts with monoamine (serotonin) metabolism, which is associated with depression.