title: Reduced stress fever is accompanied by increased glucocorticoids and reduced PGE2 in adult rats exposed to endotoxin as neonates.
abstract: Immune challenges during 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 approximately 1.5 degrees 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(-1) to 226.29+/-9.87 ng ml(-1) in nSal rats, and from 83.43+/-10.31 ng ml(-1) to 324.7+/-36.87 ng ml(-1) in nLPS rats. Animals treated with LPS as neonates and adrenalectomized one 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/PGE(2) production in preoptic/anteroventral third ventricular region (AV3V) since stress failed to cause a significant increase in PGE(2) 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 adult rats treated with LPS as neonates, and they act downregulating PGE(2) production in AV3V. 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.
authors.affiliation: Department of Physiology, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Renato N
authors.initials: RN
authors.lastname: Soriano
authors.forename: Luiz G S
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000315:Adrenalectomy / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D005334:Fever / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D005938:Glucocorticoids / Q000097:blood*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications*; D020542:Third Ventricle / Q000187:drug effects / Q000378:metabolism
chemical_list: D004731:Endotoxins; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D003907:Dexamethasone; D015232:Dinoprostone