Effects of PEG-interferon alpha plus ribavirin on tryptophan metabolism in patients with chronic hepatitis C

Comai, Stefano; Cavalletto, Luisa; Chemello, Liliana; Bernardinello, Elisabetta; Ragazzi, Eugenio; Costa, Carlo Virgilio Luigi; Bertazzo, Antonella

doi:10.1016/j.phrs.2010.10.009

Cited by 45 publications

(38 citation statements)

References 49 publications

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“…It is worth noting that patients with a history of depression were excluded from this trial and as such, they may have been measuring de novo depression in a symptom resistant population. This interpretation would seem in line with the findings in hepatitis C patients where only a subset of patients develop depression, potentially correlating with an underlying susceptibility (Comai et al, 2011). Furthermore, the relationship between K/T ratios and depressive symptoms in melanoma patients treated with IFN-α and paroxetine supports this hypothesis.…”

Section: Dysregulation Of the Kynurenine Pathway In Cns Diseasessupporting

confidence: 84%

“…Of interest within these patients, IFN-α treatment can enhance tryptophan metabolism through the KP pathway as measured by K/T ratios, an indicator of IDO activity (Capuron et al, 2003). Tryptophan was typically reduced in serum samples, though not always (Comai et al, 2011), and kynurenine levels increased during IFN-α treatment. The alteration in K/T ratios correlated with symptoms of depression and anxiety scores on the Montgomery–Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAM-A), respectively (Bonaccorso et al, 2002b).…”

Section: Dysregulation Of the Kynurenine Pathway In Cns Diseasesmentioning

confidence: 99%

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Kynurenines in CNS disease: regulation by inflammatory cytokines

et al. 2014

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The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and generates a number of neuroactive metabolites collectively called the kynurenines. Segregated into at least two distinct branches, often termed the “neurotoxic” and “neuroprotective” arms of the KP, they are regulated by the two enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively. Interestingly, several enzymes in the pathway are under tight control of inflammatory mediators. Recent years have seen a tremendous increase in our understanding of neuroinflammation in CNS disease. This review will focus on the regulation of the KP by inflammatory mediators as it pertains to neurodegenerative and psychiatric disorders.

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Section: Dysregulation Of the Kynurenine Pathway In Cns Diseasessupporting

confidence: 84%

Section: Dysregulation Of the Kynurenine Pathway In Cns Diseasesmentioning

confidence: 99%

Kynurenines in CNS disease: regulation by inflammatory cytokines

et al. 2014

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“…Cancer patients who were treated with IFN-␣ showed reduced levels of tryptophan within 1 mo of therapy, and the decrease in serum tryptophan correlated positively with the severity of depressive symptoms (15). In a study of Hep C patients treated with IFN-␣, a decrease in plasma tryptophan and an increase in kynurenine plasma levels were observed, and this in turn was associated with an increase in levels of depression in these patients (21). An alternate role for IDO in the pathogenesis of depression, independent of 5-HT synthesis, has also been postulated.…”

Section: Mood Disorders and Liver Diseasementioning

confidence: 99%

Liver-brain inflammation axis

D’Mello

Swain

2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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It is becoming increasingly evident that peripheral organ-centered inflammatory diseases, including chronic inflammatory liver diseases, are associated with changes in central neural transmission that result in alterations in behavior. These behavioral changes include sickness behaviors, such as fatigue, cognitive dysfunction, mood disorders, and sleep disturbances. While such behaviors have a significant impact on quality of life, the changes within the brain and the communication pathways between the liver and the brain that give rise to changes in central neural activity are not fully understood. Traditionally, neural and humoral communication pathways have been described, with the three cytokines TNFα, IL-1β, and IL-6 receiving the most attention in mediating communication between the periphery and the brain, in the setting of peripheral inflammation. However, more recently, we described an immune-mediated communication pathway in experimentally induced liver inflammation whereby, in response to activation of resident immune cells in the brain (i.e., the microglia), peripheral circulating monocytes transmigrate into the brain, leading to development of sickness behaviors. These signaling pathways drive changes in behavior by altering central neurotransmitter systems. Specifically, changes in serotonergic and corticotropin-releasing hormone neurotransmission have been demonstrated and implicated in liver inflammation-associated sickness behaviors. Understanding how the liver communicates with the brain in the setting of chronic inflammatory liver diseases will help delineate novel therapeutic targets that can reduce the burden of symptoms in patients with liver disease.

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“…In fact, it has been shown that brain depletion of TRP, a biochemical precursor of serotonin (5‐HT), may induce depression . On the other hand, IFN may directly affect 5‐HT synthesis via degrading enzyme indoleamine 2,3‐dioxygenase (IDO), whereas cytokines may influence 5‐HT availability by upregulation of the serotonin transporter (SERT) …”

Section: Introductionmentioning

confidence: 99%

Serotonin and its implication in the side‐effects of interferon‐based treatment of patients with chronic viral hepatitis: Pharmacological interventions

Stasi

Rosselli

Zignego

et al. 2013

Hepatology Research

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Depression is a frequent side-effect of interferon-based treatment of patients with chronic viral hepatitis, that may lead to reduction or discontinuation of treatment. Clinical trials data showed the importance of therapy of psychiatric disorders for a successful antiviral treatment. Emerging evidence suggests that interferon may cause depression affecting serotonin synthesis via increased activity of indoleamine 2,3-dioxygenase. Serotonin reuptake inhibitors significantly improve mood disorders, but the use of these drugs requires caution because some studies reported the emergence of mania in patients treated for depression during antiviral therapy. Therefore, this review will examine and discuss the putative role of serotonin and its metabolism in the development of depression during antiviral therapy, focusing on pharmacological interventions to reduce side-effects.

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Effects of PEG-interferon alpha plus ribavirin on tryptophan metabolism in patients with chronic hepatitis C

Cited by 45 publications

References 49 publications

Kynurenines in CNS disease: regulation by inflammatory cytokines

Kynurenines in CNS disease: regulation by inflammatory cytokines

Liver-brain inflammation axis

Serotonin and its implication in the side‐effects of interferon‐based treatment of patients with chronic viral hepatitis: Pharmacological interventions

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