Potentiation of tumor metastasis in adulthood by neonatal endotoxin exposure: sex differences.
Previous research in rodents has demonstrated that neonatal exposure to bacterial endotoxin alters the hypothalamic-pituitary-adrenal (HPA) axis resulting in hypersecretion of corticosterone in response to stress in adulthood. Given the known interactions between glucocorticoids and the immune system we tested the hypothesis that such alterations may impact on immune outcomes. Male and female Fischer 344 neonate rats were treated with endotoxin (0.05 mg/kg lipopolysaccaride from Salmonella enteritidis) or vehicle on days 1, 3, 5 and 7 postpartum. In adulthood, animals were subjected to chronic stress and the effect on resistance to tumor colonization (Exp. 1), natural killer (NK) cell activity (Exp. 2), and HPA reactivity (Exp. 3) was assessed. Neonatal endotoxin treatment was found to significantly impair NK cell activity and decrease resistance to tumor colonization in male but not female rats (P<0.05). Neonatal endotoxin exposure did not affect corticosterone responses to chronic stress in male or female rats, but the corticosterone response to acute stress was potentiated by endotoxin exposure, most notably in females. In conclusion, neonatal endotoxin exposure was found to be associated with a sexually differentiated impairment in tumor colonization and NK activity and long-term alterations in corticosterone responses to stress. The effect on tumor colonization and NK activity was not, however, critically mediated by corticosterone levels. These findings suggest that neonatal bacterial infections may have long-term health implications, specifically in terms of resistance to cancer spread in adulthood.
Laboratory of Neuroimmunology, School of Behavioural Sciences, University of Newcastle, Callaghan, Newcastle, New South Wales 2308, Australia. dhodgson@psychology.newcastle.edu.au
Deborah M
DM
Hodgson
Brendon
B
Knott
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D009362:Neoplasm Metastasis / Q000276:immunology / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000378:metabolism
D004731:Endotoxins; D003345:Corticosterone