Brief report Cytokine profiles in bipolar affective disorder: Focus on acutely ill patients Sinead M. O’Brien, Paul Scully, Lucinda V. Scott, Timothy G. Dinan * Alimentary Pharmabiotic Centre and Department of Psychiatry, University College Cork, Wilton, Cork, Ireland Received 5 May 2005; received in revised form 23 November 2005; accepted 25 November 2005 Available online 10 January 2006 Abstract Background: The role of the immune system in mood disorders is predominately supported by studies in unipolar major depression. However activation of the immune system has also been demonstrated in bipolar mania. Our study examines pro- inflammatory and anti-inflammatory cytokines in both phases of bipolar affective disorder (BPAD). Methods: Plasma concentrations of IL-6, IL-8, IL-10, TNF-a and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in patients with BPAD who were depressed, or manic and in healthy controls. Results: Bipolar depression had significantly higher production of the pro-inflammatory cytokines, IL-8 ( p b 0.001) and TNF-a ( p b 0.05) compared to healthy subjects. The manic group also had increased production of IL-8 ( p b 0.05) and TNF-a ( p b 0.001) as compared to healthy subjects. Anti-inflammatory cytokine levels did not differ across the 3 groups. Limitations: A small sample size was studied. All patients remained on medication for this study. Conclusions: BPAD is associated with increased production of pro-inflammatory cytokines both in the manic and in the depressed phase as compared to healthy subjects. This is the first study, which examined both mania and bipolar depression. D 2005 Elsevier B.V. All rights reserved. Keywords: Bipolar affective disorder; Psychoneuroimmunology; Cytokine; ELISA; Interleukin 1. Introduction The role of the immune system in mood disorders is predominately supported by studies in unipolar depres- sion. Major depression is associated with increased concentrations of pro-inflammatory cytokines such as interleukin-1h (IL-1h), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-a)(Maes, 1997,1999; Anis- man et al., 1999). Elevated serum levels of IL-2, IL-6, and IL-8 have been found in schizophrenia (Zhang et al., 2002; Maes et al., 2002). However the evidence supporting immune alterations in bipolar affective dis- order (BPAD) is sparse. Research to date on the role of the immune system in BPAD has largely focused on mania. Kronfol and House (1988) found impaired cell-mediated immunity as demonstrated by a reduced lymphocyte response to mitogen stimulation in mania. Su and colleagues (2002) measured peripheral blood mononuclear cell (PBMC) concentrations of IFN-g and IL-10 and found signifi- cantly lower IFN-g in patients with acute mania and subsequent remission, while IL-10 concentration was unaltered. Further evidence is provided by two studies: the activation of cell-mediated immunity has been pro- posed by a number of studies in mania. Maes et al. (1995) found that mania was characterized by higher 0165-0327/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2005.11.015 * Corresponding author. Tel.: +353 21 4920119. E-mail address: t.dinan@ucc.ie (T.G. Dinan). Journal of Affective Disorders 90 (2006) 263 – 267 www.elsevier.com/locate/jad