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.
|Data di pubblicazione:||2009|
|Titolo:||Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression|
|Autore/i:||Raison, Cl; Borisov, As; Majer, M; Drake, Df; Pagnoni, Giuseppe; Woolwine, Bj; Vogt, Gj; Massung, B; Miller, Ah|
|Codice identificativo ISI:||WOS:000263249900006|
|Codice identificativo Scopus:||2-s2.0-58349113599|
|Codice identificativo Pubmed:||18801471|
|Citazione:||Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression / Raison, Cl; Borisov, As; Majer, M; Drake, Df; Pagnoni, Giuseppe; Woolwine, Bj; Vogt, Gj; Massung, B; Miller, Ah. - In: BIOLOGICAL PSYCHIATRY. - ISSN 0006-3223. - STAMPA. - 65(2009), pp. 296-303.|
|Tipologia||Articolo su rivista|
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