Interferon-alpha–induced changes in tryptophan metabolism

Capuron, Lucile; Neurauter, Gabriele; Musselman, Dominique L.; Lawson, David H.; Nemeroff, Charles B.; Fuchs, Dietmar; Miller, Andrew H.

doi:10.1016/s0006-3223(03)00173-2

Cited by 439 publications

(106 citation statements)

References 32 publications

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“…Onset was early in the EO group, which is consistent with previous studies (Capuron and Ravaud, 1999). Neurovegetative and somatic symptoms reportedly appear early during IFN-a therapy, whereas mood and cognitive symptoms develop later (Capuron et al, 2002). Similarly, in the EO group, neurovegetative and somatic symptoms were the most common initial symptoms.…”

Section: Discussionsupporting

confidence: 89%

Nitric oxide involvement in depression during interferon-alpha therapy

Suzuki

Yoshida

Shibuya

et al. 2003

Int. J. Neuropsychopharm.

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It has been postulated that interferon induces depression via a nitric oxide-related system. The purpose of this study was to test whether there was a difference in the effects of interferon-alpha (IFN-alpha) on nitric oxide production between patients with and without interferon-induced depression. The subjects had chronic hepatitis C and were being treated with IFN-alpha. We measured plasma nitrate, a marker of nitric oxide production in vivo, before, during, and after interferon therapy. Of 146 patients, 9 developed depression within the first 4 wk of interferon therapy, and 8 developed depression later. In the former group, a significant plasma nitrate increase was observed during therapy, followed by a decrease to baseline after discontinuation. This, however, was not the case with the latter group or those who had no psychiatric symptoms. These results suggest nitric oxide involvement in at least some forms of IFN-alpha-induced depression.

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Section: Discussionsupporting

confidence: 89%

Nitric oxide involvement in depression during interferon-alpha therapy

Suzuki

Yoshida

Shibuya

et al. 2003

Int. J. Neuropsychopharm.

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“…In a small study with patients suffering from malignant melanoma, who were treated with IFN-, tryptophan concentrations decreased and neopterin levels increased in patients developing depressive symptoms [154], confirming the hypothesis that interferons might enforce the development of depression.…”

Section: Ifn--mediated Pathways and Specific Symp-toms In Hiv Infectimentioning

confidence: 65%

Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

Schroecksnadel

Zangerle

Bellmann‐Weiler

et al. 2007

CDM

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Human immunodeficiency virus type 1 (HIV) infection is characterized by progressive immunodeficiency despite of an overwhelming cellular immune activation. Patients show highly elevated serum/plasma concentrations of the proinflammatory cytokine interferon-(IFN-), which induces human monocytes to form neopterin, to produce reactive oxygen species (ROS) and in parallel, to degrade tryptophan. Enhanced tryptophan degradation by the enzyme indoleamine-2, 3-dioxygenase (IDO) contributes importantly to disease progression and "complications" of HIV infection: By a subsequent impairment of protein metabolism and serotonin formation, the development of neuropsychiatric disorders and weight loss in HIV infected patients can be enforced. Furthermore, increased IDO-activation efficiently suppresses the growth and proliferation of pathogens as well as host T-cells. IDO and other IFN--mediated pathways are strongly induced in patients with HIV infection and are also linked with disease progression: Neopterin formation by GTPcyclohydrolase I sensitively reflects the stage of the disease, and determination of the pteridine in body fluids is useful to monitor the efficacy of antiretroviral therapy. Neopterin is an independent prognostic factor for the outcome of disease, and well suited to estimate the degree of immune activation in vivo and the responsiveness of immunocompetent cells to stimulation in vitro. ROS formation may contribute to the development of oxidative stress in HIV infection, resulting in depletion of antioxidants. The cause-effective role of an overwhelming Th1-type immune response together with the activation of IDO and other IFN--mediated biochemical pathways for the course of HIV infection, the development of immunodeficiency, anemia and weight loss in HIV patients is discussed.

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“…Since then, rhIFN-α has found many applications as a therapeutic molecule in multiple myeloma [13], hairy cell leukemia [14,15,16], AIDS-related Kaposi's sarcoma [17], chronic hepatitis C [18], chronic hepatitis B [2] and condylomata acuminata [1]. Although it is effective in the therapy of its prescribed target, IFN-α has often been associated with the development of psychological manifestations, including severe depression [19,] which, however, is dose dependent [20]. …”

Section: Introductionmentioning

confidence: 99%

Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

Mehta

Mukherjee

Balasubramanian

et al. 2014

Neuroimmunomodulation

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Objective: Recombinant human interferon (rhIFN)-α is a potent immunoregulator having a wide range of therapeutic applications. In the present study, rhIFN-α was evaluated for its neuroimmunomodulatory activity. Method: Dose-dependent gene expression of cytokines and chemokines in the brain of rhIFN-administered mice was studied using real-time SYBR green PCR. Results: Statistically significant increase in expression levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1β and IFN-γ were observed. Conclusion: The findings indicate that rhIFN-α may be used at an optimized dose to cause appropriate neuromodulation of cytokine/chemokine secretion that can aid in the development of therapeutic approaches for many infectious diseases of the central nervous system for which therapies are lacking.

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Interferon-alpha–induced changes in tryptophan metabolism

Cited by 439 publications

References 32 publications

Nitric oxide involvement in depression during interferon-alpha therapy

Nitric oxide involvement in depression during interferon-alpha therapy

Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

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Interferon-alpha–induced changes in tryptophan metabolism

Cited by 439 publications

References 32 publications

Nitric oxide involvement in depression during interferon-alpha therapy

Nitric oxide involvement in depression during interferon-alpha therapy

Indoleamine-2, 3-Dioxygenase and Other Interferon-&#947;-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

Evaluation of Neuroimmunomodulatory Activity of Recombinant Human Interferon α

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Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection