Early-Life Exposure to Endotoxin Alters Hypothalamic-Pituitary-Adrenal Function and Predisposition to Inflammation

We have investigated whether exposure to Gram-negative bacterial endotoxin in early neonatal life can alter neuroendocrine and immune regulation in adult animals. Exposure of neonatal rats to a low dose of endotoxin resulted in long-term changes in hypothalamic-pituitary-adrenal (HPA) axis activity,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-05, Vol.97 (10), p.5645-5650
Main Authors: Shanks, Nola, Windle, Richard J., Perks, Paula A., Harbuz, Michael S., Jessop, David S., Ingram, Colin D., Lightman, Stafford L.
Format: Article
Language:English
Subjects:
Adult animals
Anatomy & physiology
Animals
Animals, Newborn
Arthritis
Bacteria
Biological Sciences
Corticosterone
Corticosterone - blood
Corticosterone - secretion
Disease Susceptibility
Endotoxins
Endotoxins - toxicity
Female
Handling (Psychology)
Hypothalamo-Hypophyseal System - drug effects
Hypothalamo-Hypophyseal System - pathology
Hypothalamo-Hypophyseal System - physiopathology
Inflammation
Inflammation - chemically induced
Inflammation - physiopathology
Lipopolysaccharides - toxicity
Lymphocyte Activation - drug effects
Lymphocytes
Lymphocytes - drug effects
Lymphocytes - immunology
Medical disorders
Medical research
Messenger RNA
Nervous system diseases
Pituitary-Adrenal System - drug effects
Pituitary-Adrenal System - pathology
Pituitary-Adrenal System - physiopathology
Pulse amplitude
Rats
Rats, Sprague-Dawley
Restraint, Physical
Salmonella enteritidis
Steroids
Stress, Psychological - immunology
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Summary:We have investigated whether exposure to Gram-negative bacterial endotoxin in early neonatal life can alter neuroendocrine and immune regulation in adult animals. Exposure of neonatal rats to a low dose of endotoxin resulted in long-term changes in hypothalamic-pituitary-adrenal (HPA) axis activity, with elevated mean plasma corticosterone concentrations that resulted from increased corticosterone pulse frequency and pulse amplitude. In addition to this marked effect on the development of the HPA axis, neonatal endotoxin exposure had long-lasting effects on immune regulation, including increased sensitivity of lymphocytes to stress-induced suppression of proliferation and a remarkable protection from adjuvant-induced arthritis. These findings demonstrate a potent and long-term effect of neonatal exposure to inflammatory stimuli that can program major changes in the development of both neuroendocrine and immunological regulatory mechanisms.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.090571897