Corticosterone basal levels and vulnerability to LPS-induced neuroinflammation in the rat brain.

ABSTRACT

To assess whether the individual differences on the brain response to lipopolysaccharide (LPS) are correlated with the individual differences in the hypothalamus-pituitary-adrenal axis basal activity, adult male outbred rats were injected i.p. with 1 mg/kg LPS and evaluated after 4 h. Basal (1 week before LPS) and post-LPS plasma corticosterone (CC) were measured (mean basal 225+/-22 ng/mL at 1500 h). Group H was assigned to animals with 33% higher levels of CC (>234 ng/mL) and group L to animals with 33% lower levels of CC (<167 ng/mL). The H group showed an 8.8 times less relative increase of CC after LPS than the L group as well as a reduced glucocorticoid receptor upregulation after LPS. In addition, H individuals present higher plasma levels of TNF-alpha and IL-1beta after LPS. Interestingly, these animals are more vulnerable to the accumulation of oxidative/nitrosative mediators in the brain (NF-kappaB, NOS-2 and COX-2). Concomitantly, H animals are less protected against LPS-induced neuroinflammation, since anti-inflammatory mediators, lipocalin-prostaglandinD2 synthase and peroxisome proliferator-activated gamma, are downregulated after LPS. These data demonstrate that CC plasma basal levels might be a relevant parameter for predicting the individual response to LPS.