J Affect Disord. 2008 May;108(1-2):171-6. Epub 2007 Oct 22.

IFN-gamma mediated pathways in patients with fatigue and chronic active Epstein Barr virus-infection.

Bellmann-Weiler R, Schroecksnadel K, Holzer C, Larcher C, Fuchs D, Weiss G. Department of General Internal Medicine, Clinical Immunology and Infectious Diseases, Innsbruck Medical University, Innsbruck, Austria.

BACKGROUND: Chronic active Epstein Barr virus (EBV)-infection is characterized by mononucleosis like symptoms including fatigue, lymphadenopathy and/or hepatosplenomegaly and serologic evidence for ongoing EBV replication. Interferon-gamma (IFN-gamma) triggers several antiviral mechanisms in target cells including the induction of indoleamine-2,3-dioxygenase (IDO), which degrades the essential amino acid tryptophan to kynurenine. Because tryptophan is a precursor of the neurotransmitter 5-hydroxytryptamine (serotonin), tryptophan depletion by IDO can cause mood disturbances in patients with chronic immune activation.

METHODS: This study investigated the tryptophan metabolism in 20 patients with chronic active EBV-infection, who were followed up for 4 to 8 months and in 10 healthy age-matched controls. The clinical suspicion of chronic active EBV infection was verified by the presence of circulating antibodies against EBV early antigen (EA) and virus capsid antigen (VCA).

RESULTS: Patients with detectable EBV-DNA had higher serum neopterin (p<0.01) and lower tryptophan concentrations (p=0.01) than EBV-DNA negative patients. Serum concentrations of neopterin, indicating Th-1 mediated immune activation via IFN-gamma, were positively correlated to enhanced tryptophan degradation (rs=0.650, p<0.001) in patients, but not in healthy individuals. Patients suffering from more severe symptoms (as assessed by questionnaires) tended to have aggravated tryptophan degradation.

CONCLUSION: Our data show that EBV viremia is associated with cell-mediated immune activation and increased tryptophan degradation, which may partly account for the symptoms found in this disorder.

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