Regulatory T cells increased while IL-1β decreased during antidepressant therapy.
BACKGROUND
Regulatory T cells (Tregs, CD4(+)CD25(hi)) are specialized in steering the immune response and cytokine release to maintain tolerance to self-antigens. As cytokines such as interleukin (IL)-1β, IL-6 and interferon (IFN)-α have been shown to be involved in the pathophysiology of depression and cytokine levels have been shown to change during successful antidepressant treatment, we tested the involvement CD4(+)CD25(hi) Tregs in these immunological processes during antidepressant therapy.


METHODS
16 patients suffering from a depressive episode were included into the study and treated with antidepressants according to their doctor's choice. Blood samples were collected during the first week after admission and after 6 weeks of treatment. Therein, we determined plasma levels of IL-1β, and measured IL-1β, IL-6 and IFN-α levels in the stimulated blood by performing a whole blood assay. We distinguished lymphocytes and identified CD4(+)CD25(hi) Tregs by multiparameter flow cytometry. The psychopathological status was assessed using the Hamilton Depression Rating Scale (HAMD-21).


RESULTS
HAMD-21 score, IL-1β serum levels as well as LPS-stimulated IL-1β and IL-6 production had decreased significantly at the end of treatment. In contrast, the amount of CD4(+)CD25(hi) cells increased significantly from 2.74% ± 0.88 (mean value ± standard deviation) to 3.54% ± 1.21; p = 0.007. No significant changes in virus-induced IFN-α production was observed.


CONCLUSIONS
The increase in CD4(+)CD25(hi) Tregs during antidepressant therapy may be the reason for the decrease in cytokine production and the recovery from depression.
Himmerich
Hubertus
H
Department of Psychiatry and Psychotherapy, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
Milenović
Saša
S
Fulda
Stephany
S
Plümäkers
Birgit
B
Sheldrick
Abigail J
AJ
Michel
Tanja M
TM
Kircher
Tilo
T
Rink
Lothar
L
D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*
D000928:Antidepressive Agents; D016207:Cytokines; C508017:IL2RA protein, human; D053583:Interleukin-1beta; D053645:Interleukin-2 Receptor alpha Subunit