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 ad ult 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 endotoxi n exposure had long-lasting effects on immune regulation, including increas ed sensitivity of lymphocytes to stress-induced suppression of proliferatio n and a remarkable protection from adjuvant-induced arthritis. These findin gs demonstrate a potent and long-term effect of neonatal exposure to inflam matory stimuli that can program major changes in the development of both ne uroendocrine and immunological regulatory mechanisms.