Gretchen N. Neigh, Mandakh Bekhbat, and Sydney A. Rowson
Bidirectional interactions between the immune system and central nervous system have been acknowledged for centuries. Over the past 100 years, pioneering studies in both animal models and humans have delineated the behavioral consequences of neuroimmune activation, including the different facets of sickness behavior. Rodent studies have uncovered multiple neural pathways and mechanisms that mediate anorexia, fever, sleep alterations, and social withdrawal following immune activation. Furthermore, work conducted in human patients receiving interferon treatment has elucidated some of the mechanisms underlying immune-induced behavioral changes such as malaise, depressive symptoms, and cognitive deficits.
These findings have provided the foundation for development of treatment interventions for conditions in which dysfunction of immune-brain interactions leads to behavioral pathology. Rodent models of neuroimmune activation frequently utilize endotoxins and cytokines to directly stimulate the immune system. In the absence of pathogen-induced inflammation, a variety of environmental stressors, including psychosocial stressors, also lead to neuroimmune alterations and concurrent behavioral changes. These behavioral alterations can be assessed using a battery of behavioral paradigms while distinguishing acute sickness behavior from the type of behavioral outcome being assessed. Animal studies have also been useful in delineating the role of microglia, the neuroendocrine system, neurotransmitters, and neurotrophins in mediating the behavioral implications of altered neuroimmune activity. Furthermore, the timing and duration of neuroimmune challenge as well as the sex of the organism can impact the behavioral manifestations of altered neuroimmune activity. Finally, neuroimmune modulation through pharmacological or psychosocial approaches has potential for modulating behavior.