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Long-term Effects of Neonatal Exposure to Endotoxin on the Development of Neuroendocrine-immune Interactions

Shanks, N (Division of Medicine, University of Bristol, UK)
Perks, P (Division of Medicine, University of Bristol, UK)
Lightman, SL (Division of Medicine, University of Bristol, UK)

Contact Person: N.Shanks (N.Shanks@bristol.ac.uk)


Early life environments exert long-term effects on the development of the CNS and endocrine systems and their interactions with the immune system. We have designed an animal model assessing the effects of early life inflammation on the development of the hypothalamic-pituitary- adrenal (HPA) axis and we report that neonatal exposure to endotoxin (LPS) during the first week of life alters HPA stress responsiveness in adult Sprague Dawley rats. Animals exposed to LPS (ENDO) exhibit greater behavioral reactivity and plasma corticosterone and ACTH responses to restraint stress when compared to saline treated controls (SAL). ENDO animals also exhibit greater stress-induced suppression of peripheral blood lymphocyte (PBL) and splenocyte in vitro proliferation in response to the mitogens compared to SAL animals. Differences were also observed between ENDO and SAL animals in their HPA responses to acute and chronic inflammatory challenges and in their susceptibility to inflammation associated with adjuvant -induced arthritis. These data indicate that neonatal inflammation can alter development of endocrine function, behavioral reactivity and immune-endocrine interactions. It is suggested that endocrine, nervous and immune systems are responsive to environmental factors during development and that this plasticity may alter predisposition to inflammation and stress-related pathologies. Supported by The Wellcome Trust & United Bristol Healthcare Trust

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Presentation Number SAshanks0236
Keywords: HPA, stress, endotoxin, CRH, arthritis

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Shanks, N; Perks, P; Lightman, SL; (1998). Long-term Effects of Neonatal Exposure to Endotoxin on the Development of Neuroendocrine-immune Interactions. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/anisman/shanks0236/index.html
© 1998 Author(s) Hold Copyright