Neuroendocrinology of infection and the innate immune system

This chapter deals with two topics: the evolutionary and functional implications of the effects of bacterial endotoxin on the neuroendocrine system in higher vertebrates and a newly recognized neuroendocrine mechanism of immune regulation by the direct secretion of immunoregulatory cytokines from the brain. Endotoxin is a highly specific stimulus to hypothalamic-hypophysial activity; neuroendocrine responses are integrated with behavioral, body temperature, and innate immune responses. All depend upon the genetically programmed capacity of several classes of cells to distinguish molecular patterns foreign to self that are characteristic of pathogenic microorganisms. One component of the response to endotoxin and inflammation in the brain is the direct secretion into the blood (by bulk flow) of appreciable amounts of immunoregulatory cytokines that can modify peripheral levels of IL-6 and TNF-alpha. These can arise from activated glia, endothelia, choroid plexus, and possibly specific neuronal groups. Despite its being an "immune-privileged" organ, brain-presented antigens provoke a greater humoral immune response than by other routes. The capacities of the brain to regulate peripheral cytokine levels by their direct secretion into the blood and to induce antibody response are potential pathways of peripheral neuroimmunomodulation. This mechanism is integrated with the better-established modes of neuroimmunomodulation, sympathetic nervous system, and hypothalamic-pituitary axis.