Imbalance between pro- and anti-inflammatory cytokines, and between Th1 and Th2 cytokines in depressed patients: the effect of electroacupuncture or fluoxetine treatment.
BACKGROUND
An increase in inflammatory response and an imbalance between T-helper (Th) 1 and 2 functions have been implicated in major depression. The aims of the present study were to 1) study the relationship between pro- and anti-inflammatory cytokines and between Th1 and Th2 produced cytokines in depressed patients and 2) evaluate and compare the effect of treatments with electroacupuncture (EA) and fluoxetine on these cytokines.


METHODS
95 outpatients with major depressive disorder were treated for 6 weeks with EA, fluoxetine or placebo. Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression (CGI) were used to assess severity and therapeutic effects. 30 volunteers served as controls. Serum cytokine concentrations were measured by ELISA.


RESULTS
Increased proinflammatory cytokine interleukin (IL)-1beta and decreased anti-inflammatory cytokine IL-10 were found in the depressed patients. By contract, Th1 produced proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were decreased, and Th2 produced cytokine IL-4 was significantly increased in depressed patients. The ratio of IFN/IL-4 was also increased. Both acupuncture and fluoxetine treatments, but not the placebo, reduced IL-1beta concentrations in responders. However, only acupuncture attenuated TNF-alpha concentration and INF-gamma/IL-4 ratio towards the control level.


CONCLUSIONS
These results suggest that an imbalance between the pro- and anti-inflammatory cytokines (IL-1 and IL-10), and between Th1 and Th2 cytokines (INF-gamma or TNF-alpha and IL-4) occurred in untreated depressed patients. Both EA and fluoxetine had an anti-inflammatory effect by reducing IL-1beta. EA treatment also restored the balance between Th1 and Th2 systems by increasing TNF-alpha and decreasing IL-4.
Song
C
C
Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada. cai.song@nrc.gc.ca
Halbreich
U
U
Han
C
C
Leonard
B E
BE
Luo
H
H
D000328:Adult; D000704:Analysis of Variance; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D015671:Electroacupuncture; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D018687:Antidepressive Agents, Second-Generation; D016207:Cytokines; C508609:IL10 protein, human; C508598:IL4 protein, human; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma