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.
Key Words
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Article Info
Publication History
Published online: September 19, 2008
Accepted:
August 7,
2008
Received in revised form:
July 5,
2008
Received:
February 12,
2008
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
