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

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 15:00 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-α and IL-1β after LPS. Interestingly, these animals are more vulnerable to the accumulation of oxidative/nitrosative mediators in the brain (NF-κB, 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.