Early-life exposure to endotoxin alters hypothalamic-pituitary-adrenal function and predisposition to inflammation
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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.
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Neonatal animals exposed to low-dose endotoxins showed long-term HPA axis alterations, with increased mean glucocorticoid concentrations resulting from an increase in glucocorticoid pulse frequency and amplitude.
“In addition, they showed long-term HPA axis alterations in activity, as evidenced by increased mean glucocorticoid concentrations resulting from an increase in glucocorticoid pulse frequency and amplitude.”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [365]
Exposure of neonatal animals to low-dose endotoxins resulted in activation of Toll-like receptors.
“Exposure of neonatal animals to low-dose endotoxins resulted in the activation of TLRs (364, 365).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [365]
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- Authors
- Shanks, N., Windle, R. J., Perks, P. A., Harbuz, M. S., Jessop, D. S., Ingram, C. D., & Lightman, S. L.
- Affiliations
- Bristol Royal Infirmary (GB)
- Division of Medicine, University of Bristol, Bristol Royal Infirmary Labs, Marlborough Street, Bristol, BS2 8HW, United Kingdom; and Department of Anatomy, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, United Kingdom
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-04-25
- Volume
- 97
- Issue
- 10
- Pages
- 5645-5650
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC25882
- OpenAlex
- W1986130500
- Cited by
- 374
- References
- 31
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 14 · 2020: 6 · 2019: 7 · 2018: 14 · 2017: 16 · 2016: 19 · 2015: 18 · 2014: 16 · 2013: 22 · 2012: 20
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- endotoxin, neonatal exposure, hypothalamic-pituitary-adrenal axis, corticosterone, neuroendocrine regulation, immune regulation, lymphocyte proliferation, stress-induced immunosuppression, adjuvant-induced arthritis, inflammation, developmental programming, rats
- MeSH terms
- Animals, Animals, Newborn, Corticosterone, Disease Susceptibility, Endotoxins, Female, Handling, Psychological, Hypothalamo-Hypophyseal System, Inflammation, Lipopolysaccharides, Lymphocyte Activation, Lymphocytes, Pituitary-Adrenal System, Restraint, Physical, Salmonella enteritidis, Stress, Psychological, Rats, Sprague-Dawley, Rats
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