Neonatal endotoxin exposure influences HPA responsivity and impairs tumor immunity in Fischer 344 rats in adulthood.
Recent research in rodents has demonstrated that exposure to bacterial endotoxin during the neonatal period alters the development of the hypothalamic-pituitary-adrenal axis resulting in hypersecretion of corticosterone after stress-exposure in adulthood. Given the known interactions between glucocorticoids and the immune system it was hypothesized that such alterations may impact on immune outcomes. Fischer 344 rats were treated with endotoxin (50 microg/kg Salmonella enteritidis, i.p.) or the vehicle on postpartum d 1, 3, 5, and 7. In adulthood, animals were subjected to chronic stress (6 x 10 h/d restraint stress), and the effect on resistance to tumor colonization (experiment 1) and natural killer cell activity (experiment 2) was assessed. Experiment 3 assessed corticosterone responses to acute stress in adulthood after neonatal endotoxin or saline treatment. Neonatal endotoxin exposure resulted in a 2-fold increase in tumor colonization (p < 0.001) and a significant impairment in the activity of natural killer cells (p < 0.01), cells critically involved in the surveillance and eradication of tumor cells. Neonatal endotoxin exposure also resulted in a significant decrease in gain weight that persisted into adulthood (p < 0.05), and potentiation of corticosterone responses to acute stress in adulthood (p < 0.05). We conclude that neonatal endotoxin exposure produces long-term changes in the hypothalamic-pituitary-adrenal axis, and has significant long-term effects on immune function, specifically in terms of resistance to tumor colonization in adulthood.
Hodgson
D M
DM
Laboratory of Neuroimmunology, School of Behavioural Sciences, The University of Newcastle, Callaghan, New South Wales, 2308, Australia. dhodgson@psychology.newcastle.edu.au
Knott
B
B
Walker
F R
FR
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects*; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000276:immunology; D009362:Neoplasm Metastasis / Q000276:immunology; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D012477:Salmonella enteritidis
D004731:Endotoxins