Fetal alcohol exposure (FAE) impairs the functioning of the immune system and decreases resistance to various infectious diseases. FAE also alters the development of neural and neuroendocrine systems, and thus may interfere with the bidirectional communications between the immune and the nervous system of offspring. Data indicate that FAE impairs the interactions between the immune and nervous systems. For example, we have shown that FAE blunts the febrile response induced by a pathogen product, lipopolysaccharide (LPS), and one of the cytokines, interleukin-1 beta (IL1), induced by LPS. Moreover, maternal adrenalectomy was found to prevent the blunted febrile response. The effects of FAE are probably mediated by developmentally-induced alterations in brain mechanisms, since FAE also blunts the febrile response following intracerebroventricular (icv) administration of IL1. Given the essential role of fever in the host defense response to infection, we hypothesize that the attenuated febrile response following FAE reflects a general impairment in neuroimmune interactions which may contribute to the predisposition to infection resulting from FAE. One corollary hypothesis states that FAE affects the adult expression of neural mediators of the febrile component of the acute phase response to infection. A second corollary hypothesis states that prevention of FAE-induced alterations in neuroimmune interactions mediating the febrile response to LPS can be achieved by hormonal manipulations pre-or postnatally. Specifically, we aim to: 1) Characterize the effects of LPS administered ip on certain mediators of the febrile response in adult male fetal alcohol-exposed and control rats, i.e., a) prostaglandin E2 (PGE), b) norepinephrine (NE), c) nitric oxide (NO), d) arginine vasopressin (AVP), e) alpha-melanocyte stimulating hormone (MSH), f) ACTH and corticosterone and g) IL1; 2) Investigate a possible role for neonatal or adult testosterone levels in mediating the effects of FAE on the LPS-induced febrile response and on its neurochemical mediators, as identified in Aim 1; and 3) Determine whether the prevention of the blunted LPS-induced febrile response by maternal adrenalectomy is (a) mediated by adreno-medullary or -cortical products, (b) is accompanied by changes in any of the neurochemical mediators of the febrile response identified as being affected by FAE in Aim 1, and (c) is accompanied by a reversal of the FAE-induced reduction in testosterone levels in neonatal and/or adult rats.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
3R01AA009850-06S1
Application #
6503330
Study Section
Special Emphasis Panel (ZRG1 (01))
Program Officer
Foudin, Laurie L
Project Start
1994-07-01
Project End
2003-03-31
Budget Start
2001-09-28
Budget End
2003-03-31
Support Year
6
Fiscal Year
2001
Total Cost
$20,000
Indirect Cost
Name
University of California Los Angeles
Department
Neurosciences
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Taylor, Anna N; Tio, Delia L; Bando, Jennifer K et al. (2006) Differential effects of alcohol consumption and withdrawal on circadian temperature and activity rhythms in Sprague-Dawley, Lewis, and Fischer male and female rats. Alcohol Clin Exp Res 30:438-47
Taylor, Anna N; Tio, Delia L; Romeo, Horacio E (2005) The febrile response to intraperitoneal lipopolysaccharide: strain and gender differences in rats. J Neuroimmunol 158:86-93
Romeo, Horacio E; Tio, Delia L; Taylor, Anna N (2003) Effects of glossopharyngeal nerve transection on central and peripheral cytokines and serum corticosterone induced by localized inflammation. J Neuroimmunol 136:104-11
Taylor, Anna N; Romeo, Horacio E; Beylin, Anna V et al. (2002) Alcohol consumption in traumatic brain injury: attenuation of TBI-induced hyperthermia and neurocognitive deficits. J Neurotrauma 19:1597-608
Taylor, Anna N; Tio, Delia L; Heng, Ngy S et al. (2002) Alcohol consumption attenuates febrile responses to lipopolysaccharide and interleukin-1 beta in male rats. Alcohol Clin Exp Res 26:44-52
Taylor, Anna N; Tritt, Susan H; Tio, Delia L et al. (2002) Maternal adrenalectomy abrogates the effect of fetal alcohol exposure on the interleukin-1beta-induced febrile response: gender differences. Neuroendocrinology 76:185-92
Romeo, H E; Tio, D L; Rahman, S U et al. (2001) The glossopharyngeal nerve as a novel pathway in immune-to-brain communication: relevance to neuroimmune surveillance of the oral cavity. J Neuroimmunol 115:91-100
Hodgson, D M; Yirmiya, R; Taylor, A N (2001) Intracerebroventricular interleukin-1beta impairs clearance of tumor cells from the lungs: role of brain prostaglandins. J Neuroimmunol 119:57-63
Hodgson, D M; Taylor, A N; Zhang, Z et al. (1999) Lysosphingomyelin prevents behavioral aberrations and hippocampal neuron loss induced by the metabotropic glutamate receptor agonist quisqualate. Prog Neuropsychopharmacol Biol Psychiatry 23:877-92
Hodgson, D M; Yirmiya, R; Chiappelli, F et al. (1999) Intracerebral interleukin-1beta impairs response to tumor invasion: involvement of adrenal catecholamines. Brain Res 816:200-8

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