Long-term alterations in neuroimmune responses after neonatal exposure to lipopolysaccharide.
Fever is an integral part of the host's defense to infection that is orchestrated by the brain. A reduced febrile response is associated with reduced survival. Consequently, we have asked if early life immune exposure will alter febrile and neurochemical responses to immune stress in adulthood. Fourteen-day-old neonatal male rats were given Escherichia coli lipopolysaccharide (LPS) that caused either fever or hypothermia depending on ambient temperature. Control rats were given pyrogen-free saline. Regardless of the presence of neonatal fever, adult animals that had been neonatally exposed to LPS displayed attenuated fevers in response to intraperitoneal LPS but unaltered responses to intraperitoneal interleukin 1beta or intracerebroventricular prostaglandin E(2). The characteristic reduction in activity that accompanies fever was unaltered, however, as a function of neonatal LPS exposure. Treatment of neonates with an antigenically dissimilar LPS (Salmonella enteritidis) was equally effective in reducing adult responses to E. coli LPS, indicating an alteration in the innate immune response. In adults treated as neonates with LPS, basal levels of hypothalamic cyclooxygenase 2 (COX-2), determined by semiquantitative Western blot analysis, were significantly elevated compared with controls. In addition, whereas adult controls responded to LPS with the expected induction of COX-2, adults pretreated neonatally with LPS responded to LPS with a reduction in COX-2. Thus, neonatal LPS can alter CNS-mediated inflammatory responses in adult rats.
Boissé
Lysa
L
Calgary Brain Institute, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
Mouihate
Abdeslam
A
Ellis
Shaun
S
Pittman
Quentin J
QJ
D000818:Animals; D000831:Animals, Newborn; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000008:administration & dosage; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000276:immunology*; D007031:Hypothalamus / Q000378:metabolism; D007375:Interleukin-1 / Q000008:administration & dosage; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D015213:Neuroimmunomodulation / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time
D007375:Interleukin-1; D007527:Isoenzymes; D008070:Lipopolysaccharides; C433788:lipopolysaccharide, E. coli O26-B6; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone