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The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression - and other conditions characterized by tryptophan depletion induced by inflammation.

Maes M, Mihaylova I, Ruyter M, Kubera M, Bosmans E.
Journal Article 2007; 28(6): 826-831 PubMed PMID: 18063923 Citation  Keywords:  Adult, Anti-Inflammatory Agents:immunology, Cytokines:immunology, Depressive Disorder:metabolism, Female, Gene Expression Regulation:immunology, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase:immunology, Inflammation:metabolism, Interferon-gamma:immunology,.   

: Immune activation is accompanied by induction of indoleamine (2,3)-dioxygenase (IDO), an enzyme which degrades tryptophan, a phenomenon which plays a role in the pathophysiology of major depression and post-natal depression and anxiety states. TRYCATs - tryptophan catabolites along the IDO pathway - such as kynurenine, kynurenic acid, xanthurenic acid, and quinolinic acid, have multiple effects, e.g. apoptotic, anti- versus pro-oxidant, neurotoxic versus neuroprotective, and anxiolytic versus anxiogenic effects. The aim of the present study was to study the immune effects of the above TRYCATS. Toward this end we examined the effects of the above TRYCATs on the LPS + PHA-induced production of interferon-gamma (IFNgamma), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNFalpha) in 18 normal volunteers. We found that the production of IFNgamma was significantly decreased by all 4 catabolites. Xanthurenic acid and quinolinic acid decreased the production of IL-10. Kynurenine, kynurenic acid, and xanthurenic acid, decreased the IFNgamma/IL-10 production ratio, whereas quinolinic acid increased this ratio. Kynurenic acid significantly reduced the stimulated production of TNFalpha. It is concluded that kynurenine, kynurenic acid, and xanthurenic acid have anti-inflammatory effects trough a reduction of IFNgamma, whereas quinolinic acid has pro-inflammatory effects in particular via significant decreases in IL-10. Following inflammation-induced IDO activation, some TRYCATs, i.e. kynurenine, kynurenic acid, and xanthurenic acid, exert a negative feedback control over IFNgamma production thus downregulating the initial inflammation, whereas an excess of quinolinic acid further aggravates the initial inflammation....

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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.

Maes M, Mihaylova I, Kubera M, Bosmans E.
Comparative Study 2007; 28(6): 875-880 PubMed PMID: 18063921 Citation  Keywords:  Adult, Analysis of Variance, Arachidonic Acid:administration & dosage, Cytokines:immunology, Depression:drug therapy, Docosahexaenoic Acids:administration & dosage, Dose-Response Relationship, Drug, Eicosapentaenoic Acid:administration & dosage, Female, H.   

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).

AIM: 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.

DISCUSSION: 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....

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