Neonatal LPS exposure reduces stress fever in adult rats: modulation by glucocorticoids and PGE₂

Immune challenges during the neonatal period may permanently program immune responses later in life, including endotoxin fever. We tested the hypothesis that neonatal endotoxin exposure affects stress fever in adult rats. In control rats (treated with saline as neonates; nSal) body temperature peaked ~1.5°C during open-field stress, whereas in rats exposed to endotoxin (lipopolysaccharide, LPS) as neonates (nLPS) stress fever was significantly attenuated. Following stress, plasma corticosterone levels significantly increased from 74.29 ± 7.05 ng/ml to 226.29 ± 9.87 ng/ml in nSal rats, and from 83.43 ± 10.31 ng/ml to 324.7 ± 36.87 ng/ml in nLPS rats. Animals treated with LPS as neonates and adrenalectomized 1 week before experimentation no longer displayed the attenuated febrile response to stress. This attenuated stress fever caused by an increased corticosterone secretion is likely to be linked to an inhibitory effect of glucocorticoids on cyclooxygenase activity/PGE₂ production in the preoptic/anteroventral third ventricular region (AV3V) since stress failed to cause a significant increase in PGE₂ in nLPS rats, and this effect was reverted by adrenalectomy. Altogether, the present results indicate that endogenous glucocorticoids are key modulators of the attenuated stress fever in adults rats treated with LPS as neonates, and they act downregulating PGE₂ production. Moreover, our findings also support the notion that neonatal immune stimulus affects programming of stress responses during adulthood, despite the fact that inflammation and stress are two distinct processes mediated largely by different neurobiological mechanisms.