Why fish oils may not always be adequate treatments for depression or other inflammatory illnesses: docosahexaenoic acid, an omega-3 polyunsaturated fatty acid, induces a Th-1-like immune response.
BACKGROUND
We have shown that a depletion of omega3 polysaturated fatty acids (PUFAs) plays a role in the pathophysiology of depression, in part because omega3 PUFAs have anti-inflammatory effects. omega3 PUFAs are frequently employed to treat depression. Most if not all antidepressants have negative immunoregulatory effects by decreasing the production of proinflammatory cytokines, such as interferon-gamma (IFNgamma) and/or increasing that of anti-inflammatory cytokines, such as interleukin10 (IL-10).


OBJECTIVE
The aim of the present study was to examine the immunoregulary effects of the omega3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the omega6 PUFA, arachidonic acid (AA), on the production of interferon-gamma (IFNgamma), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNFalpha).


METHODS
This study examines the ex vivo effects of EPA (4.5 microM, 9 microM, 18 microM and 45 microM), DHA (1.3 microM, 3 microM, 6 microM and 13 microM) and AA (8 microM, 16 microM, 32 microM and 80 microM) on the LPS + PHA-stimulated production of IFNgamma, IL-10 and TNFalpha, and on the IFNgamma/IL-10 production ratio.


RESULTS
We found that EPA did not have any significant effects on the above cytokines. DHA significantly increased the IFNgamma/IL-10 production ratio, caused by a greater reduction in IL-10 than in IFNgamma. AA significantly decreased TNFalpha production.


CONCLUSIONS
The results show that DHA induces a Th-1-like immune response and that AA has anti-inflammatory effects by decreasing the production of TNFalpha. Thus, the immune effects of omega3 PUFAs are not compatible with what is expected from antidepressive substances. The results of the present study show that treatment with fish oils, containing DHA, should be avoided in the treatment of depression. Toward this end, highly concentrated and pure EPA seems to be indicated.
Clinical Research Center for Mental Health, Antwerp, Belgium. crc.mh@telenet.be
Michael
M
Maes
Ivanka
I
Mihaylova
Marta
M
Kubera
Eugene
E
Bosmans
D000328:Adult; D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D003863:Depression / Q000188:drug therapy / Q000276:immunology; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008297:Male; D012016:Reference Values; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D007371:Interferon-gamma; D015118:Eicosapentaenoic Acid