Human and animals studies have established that fetal alcohol exposure (FAE) is associated with significant impairments in cellular immune functions and marked disturbances in the interactions between the nervous, endocrine and immune systems. These observations have important clinical implications suggesting that FAE may lead to profound impairments in those aspects of the immune response that are most crucial for initiating, regulating, and sustaining immune surveillance against minor as well as lethal infectious agents, and against malignancies. FAE is a prenatal intervention, with effects on maternal and fetal glucocorticoids and long-term effects on neuro-endocrine-immune outcomes The marked effects of FAE upon neuro-endocrine-immune function that mediate many of the host's defense responses to infections in animal models are the subject of this review. Specifically FAE attenuates central nervous system (CNS)-mediated responses to immune challenges such as lipopolysaccharide (LPS) and interleukin (IL)-1-beta, including sympathetic outflow to the spleen, thermoregulatory and neuroendocrine processes and sickness behavior. Ethanol may have significant effects on the fetus either by a direct toxic effect during critical periods of development or because of the stress response it induces in the pregnant female. Maternal adrenalectomy in Sprague-Dawley rats or genetic impairment of hypothalamic-pituitary-adrenal (HPA) function, as in Lewis rats, were found to reverse the effects of prenatal ethanol on neuro-endocrine-immune responses in the offspring. These experimental studies suggest that activation of the maternal HPA axis may play a role in the developmental and long-term effects of ethanol.
Bibliographical noteFunding Information:
We are grateful to Delia L.Tio for her expert assistance in our studies. Our work reported herein was supported by grants from the Department of Veterans Affairs Medical Research Service, the NIAAA-NIH, and the United States-Israel Binational Science Foundation.
- Febrile acute-phase response
- Fetal alcohol exposure
- Hypothalamic-pituitary-adrenal axis