Activation of the hypothalamic-pituitary-adrenal axis and autonomic nervous system during inflammation and altered programming of the neuroendocrine-immune axis during fetal and neonatal development: lessons learned from the model inflammagen, lipopolysaccharide.

The hypothalamic-pituitary-adrenal axis (HPAA) and autonomic nervous system (ANS) are both activated during inflammation as an elaborate multi-directional communication pathway designed to restore homeostasis, in part, by regulating the inflammatory and subsequent immune response. During fetal and neonatal development programming of the HPAA, ANS and possibly the immune system is influenced by signals from the surrounding environment, as part of an adaptive mechanism to enhance the survival of the offspring. It is currently hypothesized that if this programming is either misguided, or the individual's environment is drastically altered such that neuroendocrine programming becomes maladaptive, it may contribute to the pathogenesis of certain diseases. Current research, suggests that exposure to inflammatory signals during critical windows of early life development may influence the programming of various genes within the neuroendocrine-immune axis. This review will provide, (1) an overview of the HPAA and ANS pathways that are activated during inflammation, highlighting studies that have used lipopolysaccharide as a model inflammagen and, (2) evidence to support the hypothesis that inflammatory stress during fetal and neonatal development can alter programming of the neuroendocrine-immune axis, influencing stress and immune responsiveness, and possibly disease resistance later in life.