178. Interferon-alpha-induced fatigue is associated with alterations in CNS glutamate metabolism as measured by magnetic resonance spectroscopy

Abstract

Peripheral inflammatory states and their behavioral consequences including fatigue have been well-documented. One mechanism that may contribute to inflammation-induced behavioral changes is alterations in central nervous system (CNS) glutamate metabolism. To examine the role of CNS glutamate in inflammation-induced fatigue, proton magnetic resonance spectroscopy ( MRS ) was conducted in 12 patients with hepatitis C (HCV) before and after 4 weeks of treatment with interferon ( IFN )- alpha compared to 12 HCV patients awaiting IFN-alpha therapy. IFN-alpha is an inflammatory cytokine well-known to induce symptoms of fatigue in a high percentage of patients. Compared to controls, the glutamate /creatine ratio in the left basal ganglia significantly increased following 4 weeks of IFN-alpha administration ( p < 0.05). This increase in the glutamate /creatine ratio was in turn significantly correlated with increases in fatigue severity ( r = 0.435, p = 0.034). Increased glutamate concentrations in the left basal ganglia are consistent with previously reported alterations in basal ganglia function following IFN-alpha treatment in cancer patients and patients with HCV. The data are also consistent with changes in basal ganglia function in healthy volunteers administered immune stimuli including endotoxin or typhoid vaccination. These data suggest that altered glutamate metabolism possibly as a result of altered glial function may contribute to basal ganglia changes following acute and chronic immune activation.