Quinolinic acid is an excitotoxic
kynurenine pathway metabolite, the concentration of which increases in human brain during immune activation. The present study compared
quinolinate responses to systemic and brain immune activation in gerbils and rats. Global
cerebral ischemia in gerbils, but not rats, increased hippocampus indoleamine-2,3-dioxygenase activity and
quinolinate levels 4 days postinjury. In a rat focal
ischemia model, small increases in
quinolinate concentrations occurred in infarcted regions on days 1, 3, and 7, although concentrations remained below serum values. In gerbils, systemic immune activation by an
intraperitoneal injection of
endotoxin (1 mg/kg of
body weight) increased
quinolinate levels in brain, blood, lung, liver, and spleen, with proportional increases in lung indoleamine-2,3-dioxygenase activity at 24 h postinjection. In rats, however, no significant
quinolinate content changes occurred, whereas lung indoleamine-2,3-dioxygenase activity increased slightly. Gerbil, but not rat, brain microglia and peritoneal monocytes produced large quantities of [13C(6)]-
quinolinate from L-[13C(6)]
tryptophan. Gerbil astrocytes produced relatively small quantities of
quinolinate, whereas rat astrocytes produced no detectable amounts. These results demonstrate that the limited capacity of rats to replicate elevations in brain and blood
quinolinic acid levels in response to immune activation is attributable to blunted increases in local indoleamine-2,3-dioxygenase activity and a low capacity of microglia, astrocytes, and macrophages to convert
L-tryptophan to
quinolinate.