PMID- 18801471
OWN - NLM
STAT- MEDLINE
DCOM- 20090410
LR  - 20231105
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 65
IP  - 4
DP  - 2009 Feb 15
TI  - Activation of central nervous system inflammatory pathways by interferon-alpha: 
      relationship to monoamines and depression.
PG  - 296-303
LID - 10.1016/j.biopsych.2008.08.010 [doi]
AB  - 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 approximately 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 
      (r(2) = -.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.
FAU - Raison, Charles L
AU  - Raison CL
AD  - Department of Psychiatry and Behavioral Sciences, Emory University School of 
      Medicine, Atlanta, Georgia, USA.
FAU - Borisov, Andrey S
AU  - Borisov AS
FAU - Majer, Matthias
AU  - Majer M
FAU - Drake, Daniel F
AU  - Drake DF
FAU - Pagnoni, Giuseppe
AU  - Pagnoni G
FAU - Woolwine, Bobbi J
AU  - Woolwine BJ
FAU - Vogt, Gerald J
AU  - Vogt GJ
FAU - Massung, Breanne
AU  - Massung B
FAU - Miller, Andrew H
AU  - Miller AH
LA  - eng
GR  - M01 RR0039/RR/NCRR NIH HHS/United States
GR  - K23 MH064619/MH/NIMH NIH HHS/United States
GR  - R01 MH070553/MH/NIMH NIH HHS/United States
GR  - M01 RR000039/RR/NCRR NIH HHS/United States
GR  - K05 MH069124-05/MH/NIMH NIH HHS/United States
GR  - R01 HL073921/HL/NHLBI NIH HHS/United States
GR  - T32 MH020018/MH/NIMH NIH HHS/United States
GR  - K05 MH069124/MH/NIMH NIH HHS/United States
GR  - UL1 TR000454/TR/NCATS NIH HHS/United States
GR  - R01 MH060723-04/MH/NIMH NIH HHS/United States
GR  - R01 MH060723/MH/NIMH NIH HHS/United States
GR  - UL1 RR025008/RR/NCRR NIH HHS/United States
GR  - R01 MH070553-05/MH/NIMH NIH HHS/United States
GR  - R01 HL073921-05/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20080918
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Antiviral Agents)
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Interferon-alpha)
RN  - 49717AWG6K (Ribavirin)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
SB  - IM
MH  - Adult
MH  - Antiviral Agents/pharmacology
MH  - Biogenic Monoamines/cerebrospinal fluid/*physiology
MH  - Biomarkers/analysis
MH  - Central Nervous System/*drug effects/*pathology
MH  - Corticotropin-Releasing Hormone/cerebrospinal fluid
MH  - Cytokines/cerebrospinal fluid
MH  - Depressive Disorder/cerebrospinal fluid/*pathology
MH  - Female
MH  - Humans
MH  - Inflammation/cerebrospinal fluid/*pathology
MH  - Interferon-alpha/*pharmacology
MH  - Longitudinal Studies
MH  - Male
MH  - Neural Pathways/*drug effects/*pathology
MH  - Psychiatric Status Rating Scales
MH  - Ribavirin/pharmacology
PMC - PMC2655138
MID - NIHMS92346
EDAT- 2008/09/20 09:00
MHDA- 2009/04/11 09:00
PMCR- 2010/02/15
CRDT- 2008/09/20 09:00
PHST- 2008/02/12 00:00 [received]
PHST- 2008/07/05 00:00 [revised]
PHST- 2008/08/07 00:00 [accepted]
PHST- 2008/09/20 09:00 [pubmed]
PHST- 2009/04/11 09:00 [medline]
PHST- 2008/09/20 09:00 [entrez]
PHST- 2010/02/15 00:00 [pmc-release]
AID - S0006-3223(08)00969-4 [pii]
AID - 10.1016/j.biopsych.2008.08.010 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2009 Feb 15;65(4):296-303. doi: 10.1016/j.biopsych.2008.08.010. 
      Epub 2008 Sep 18.