Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder.
BACKGROUND
The neurobiology of bipolar disorder is not completely understood. Cytokines have received increasing attention as potential mediators of the interaction with immune, neuroendocrine system and specific pathways involved in mood, energy, and activity control. Previous reports have suggested the association of mania and bipolar depression with a proinflammatory state. However, they did not compare cytokine levels in all phases of bipolar disorder.


METHODS
Sixty-one bipolar patients were recruited for assessment of serum cytokine levels. Of these, 14 were in euthymic state, 23 and 24 were in manic and depressive episodes, respectively. A healthy comparison group included 25 healthy volunteers. Cytokines involved in Th1/Th2 balance, such as TNF-alpha, IL-2, IL-4, IL-6, IL-10, IFN-gamma, were examined by flow cytometry.


RESULTS
During mania, proinflammatory cytokines, IL-2, IL-4 and IL-6, were increased in comparison with healthy subjects. Patients in depressive episode showed only increased IL-6 levels. There were no significant differences in cytokine levels between patients in remission and healthy subjects, except for IL-4. Mood symptoms showed a positive correlation with IL-6 and IL-2.


CONCLUSIONS
These findings suggest that mania, and to a less extent, depression are associated with a proinflammatory state. These changes seem to be related to mood state, as changes in cytokine profile were more pronounced during acute episodes than in euthymia. This study provides further support to investigate the immune system as a target for future treatment development.
Brietzke
Elisa
E
Bipolar Disorder Program and Molecular Psychiatry Unit, Hospital de Clínicas de Porto Alegre, UFRGS, Brazil.
Stertz
Laura
L
Fernandes
Brisa Simões
BS
Kauer-Sant'anna
Marcia
M
Mascarenhas
Marcello
M
Escosteguy Vargas
Andréia
A
Chies
José Artur
JA
Kapczinski
Flávio
F
D000328:Adult; D001288:Attention; D001714:Bipolar Disorder / Q000097:blood*; D003865:Major Depressive Disorder / Q000097:blood*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000097:blood*; D017471:Receptors, Interferon / Q000097:blood; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000096743:Interferon gamma Receptor
D016753:Interleukin-10; D007376:Interleukin-2; D015847:Interleukin-4; D015850:Interleukin-6; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor