Vertebrate sickness behaviors: Adaptive and integrated neuroendocrine immune responses

Vertebrate sickness behaviors, which include lethargy, anorexia, and decreased libido, can facilitate defense against pathogens by conserving energy for use in other immune responses and by limiting parasites' access to nutrients. Such benefits come with considerable costs, however, as lethargy decreases the time available for other fitness-enhancing activities and dampened libido directly reduces reproductive prospects. While the degree of sickness behaviors expressed varies among individuals, populations, and species, the ecological and physiological factors driving this diversity remain unclear. Here, we consider how an organism's ecological context and life-history strategy may impact the ways in which it balances the costs and benefits of sickness behaviors to enable or suppress its expression. Striking an appropriate balance requires physiological assimilation of information about external ecological conditions as well as about the status of infection and host nutrition. This integration requires multi-directional communication among the endocrine, nervous, and immune systems, the purview of the field of psychoneuroimmunology. This discipline portrays cytokines, signaling molecules originally characterized solely by their roles within the immune system, as key mediators of a brain-immune network that ensures the adaptive expression of sickness behaviors. Study of these molecules and the behaviors they coordinate in an ecological context will greatly augment our understanding of the natural variation in immune function found among wild animals.