TY - JOUR

T1 - Elevated levels of IL-6 and IL-18 in manic and hypomanic states in rapid cycling bipolar disorder patients

AU - Munkholm, Klaus

AU - Weikop, Pia

AU - Kessing, Lars Vedel

AU - Vinberg, Maj

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2015/1

Y1 - 2015/1

N2 - Inflammatory system dysregulation may be involved in the pathophysiology of bipolar disorder with peripheral cytokine levels varying between affective states; however, the evidence is based primarily on case-control studies and limited by methodological issues. The objectives of the present study were to assess alterations of peripheral cytokine levels between affective states in rapid cycling bipolar disorder patients and to compare these with levels in healthy control subjects. In a longitudinal design, repeated measurements of plasma levels of IL-6, IL-10, IL-18, IL-1β and TNF-α were obtained in affective states of varying polarity during 6-12 months in 37 rapid cycling bipolar disorder patients and compared with repeated measurements in 40 age- and gender matched healthy control subjects, using rigorous laboratory-, clinical- and statistical methodology. Adjusting for demographical, clinical- and lifestyle factors, levels of IL-6 (p<0.05) and IL-18 (p<0.005) were significantly elevated in rapid cycling bipolar disorder patients in a manic/hypomanic state, compared with a depressed and a euthymic state. Compared with healthy control subjects, unadjusted levels of IL-6 (p<0.05) and IL-18 (p<0.05) were elevated in manic/hypomanic bipolar disorder patients. Levels of IL-10 and IL-1β were undetectable in the majority of samples; high TNF-α assay variability was found. The results support a role for altered peripheral immune response signaling in rapid cycling bipolar disorder and suggest that IL-6 and IL-18 could be markers of manic episodes.

AB - Inflammatory system dysregulation may be involved in the pathophysiology of bipolar disorder with peripheral cytokine levels varying between affective states; however, the evidence is based primarily on case-control studies and limited by methodological issues. The objectives of the present study were to assess alterations of peripheral cytokine levels between affective states in rapid cycling bipolar disorder patients and to compare these with levels in healthy control subjects. In a longitudinal design, repeated measurements of plasma levels of IL-6, IL-10, IL-18, IL-1β and TNF-α were obtained in affective states of varying polarity during 6-12 months in 37 rapid cycling bipolar disorder patients and compared with repeated measurements in 40 age- and gender matched healthy control subjects, using rigorous laboratory-, clinical- and statistical methodology. Adjusting for demographical, clinical- and lifestyle factors, levels of IL-6 (p<0.05) and IL-18 (p<0.005) were significantly elevated in rapid cycling bipolar disorder patients in a manic/hypomanic state, compared with a depressed and a euthymic state. Compared with healthy control subjects, unadjusted levels of IL-6 (p<0.05) and IL-18 (p<0.05) were elevated in manic/hypomanic bipolar disorder patients. Levels of IL-10 and IL-1β were undetectable in the majority of samples; high TNF-α assay variability was found. The results support a role for altered peripheral immune response signaling in rapid cycling bipolar disorder and suggest that IL-6 and IL-18 could be markers of manic episodes.

U2 - 10.1016/j.bbi.2014.09.021

DO - 10.1016/j.bbi.2014.09.021

M3 - Journal article

C2 - 25451609

VL - 43

SP - 205

EP - 213

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

SN - 0889-1591

ER -