Neuro-immune mechanisms of fatigue and fever

Abstract

Acute viral infection associates fatigue and fever. Using an animal model of viral infection, we studied molecules and neural substrates possibly involved in fever and fatigue. In the animal model, rats or mice were injected intraperitoneally with poly IC, a synthetic double-stranded RNA, as a viral mimic. Animals received poly IC developed fever and showed a decrease in locomotor activity during the dark period, which we used as an index of fatigue. Fever was completely suppressed by a prostaglandin (PG)-synthesis inhibitor. On the other hand, the inhibitor partially suppressed fatigue in the early phase (18:00-24:00) of the dark period, and failed to reduce fatigue in the late phase (24:00-6:00). These results indicate that poly IC-induced fatigue consists of PG-dependent and PG-independent mechanisms. We next examined neurons possibly involved in poly IC-induced fatigue using Fos as a neuronal activity marker. Three hours after poly IC injection, the numbers of Fos-positive neurons were increased in the ventromedial preoptic nucleus (VMPO), hypothalamic paraventricular nucleus (PVN), bed nucleus of stria terminalis (BNST), central nucleus of amygdala (CeA), lateral parabrachial nucleus (LPBN), and nucleus of solitary tract (NTS). The PG-synthesis inhibitor suppressed Fos expression in VMPO, PVN, LPBN and NTS, but did not suppress Fos expression in BNST and CeA. These brain loci may be involved in PG-dependent and PG-independent fatigue, respectively. [J Physiol Sci. 2008;58 Suppl:S19]