The energetics of immunity: a neuroendocrine link between energy balance and immune function
Introduction
Among the many significant contributions Frank A. Beach made to the field of behavioral endocrinology, particularly influential was his emphasis on the importance of integration in scientific pursuits; Beach believed that to fully understand physiology and behavior, one needed to understand not only the interrelationships among behavior and the nervous and endocrine systems, but also the complex dynamics that occur within the ecological context of the environment in which an animal lives. Furthermore, the mechanisms of behavior must also be understood in an evolutionary framework. Thus, it was Beach's strong belief that an “integrative psychobiology would transcend all levels of analysis” and would be “rooted in the study of its physiological correlates on the one hand and its adaptive function on the other” (Dewsbury, 1988). As students of behavioral neuroendocrinology, application of an integrative approach to the study of hormones, brain, and behavior remains one of our greatest challenges. This review will focus on how an integrative approach to the study of neuroendocrine–immune interactions can be useful in addressing important questions regarding the neural and hormonal mechanisms underlying the energetic regulation of immunity.
Section snippets
A role for immune function in behavioral neuroendocrinology
Vertebrate species rely on three physiological systems for cell–cell communication: the nervous, endocrine, and immune systems. Despite their unique labels and associated nomenclature, these three signaling systems do not operate in a vacuum. Rather, as the field of behavioral neuroendocrinology has consistently demonstrated, the nervous and endocrine systems interact with one another at several important physiological levels and the functions of either system depend on the status of the other
Energetic trade-offs
As the age-old adage “feed a cold, starve a fever” suggests, there is an important biological link between energy balance and immune function and thus, disease susceptibility. Immunity, like all other physiological processes, requires adequate energy to sustain optimal functioning. Despite this obvious fact, the role of energy balance has only recently begun to be considered in the context of immune function and disease. Within the last few years, the concept of energetic “trade-offs” among
Adipose tissue and immunity
Despite the apparent link between energy availability and immunity, relatively little is known regarding the physiological mechanisms by which energy regulates immune function. On one hand, a chronic positive imbalance between energy intake and expenditure leads to obesity and can impair immune function and increase disease susceptibility in both clinical populations and genetically obese animal models (Marti et al., 2001). On the other hand, marked reductions in energy availability without
Body fat and immunity: lessons from seasonally breeding animals
Seasonally breeding rodents provide an excellent model with which to study the role of energy balance in the regulation of immunity because the majority of these species undergo substantial, naturally occurring fluctuations in total body fat throughout the year (reviewed in Bartness and Wade, 1985, Bartness et al., 2002). In addition, most rodent species studied to date display seasonal changes in immune function that are, in general, positively correlated with their energy stores. The exact
Leptin: a neuroendocrine link between adipose tissue and immunity
The studies reviewed above suggest that body fat plays an important role in regulating immune function in many vertebrate species. However, the precise neuroendocrine mechanisms by which energy availability is translated into a physiological signal indicating current energy balance are not fully understood. In the past few years alone, however, a variety of endocrine factors have been identified as potential candidates for providing biochemical signals of current energy availability (reviewed
A role for the sympathetic nervous system?
Although many of the effects of leptin on the regulation total body fat are due to the effects of this hormone on food intake, an increasing number of studies suggest that the actions of leptin on energy balance are due, at least in part, to activation of the sympathetic nervous system (SNS) and subsequent increases in metabolism Elmquist, 2001, Mizuno et al., 1998, Rayner, 2001, Scarpace et al., 2000. Furthermore, stimulation of the leptin system increases sympathetic activity in a variety of
The future of “psychoneuroimmunoendocrinology”
Although significant progress has been made in our understanding of the energetic regulation of immunity, many important questions still remain. For example, we are just beginning to identify the wide array of endocrine and nervous system factors involved in the metabolic regulation of immune function. In addition, much less is known about the mechanisms by which the immune system, in turn, communicates with metabolic systems to inform the body of current immunological requirements relative to
Acknowledgements
I would like to acknowledge Randy Nelson, Gregory Ball and Timothy Bartness for all of their guidance and encouragement during my graduate and postdoctoral training. I would also like to thank Joseph Casto, Debbie Drazen, Alicia Faruzzi, Aaron Jasnow, Sabra Klein, Lance Kriegsfeld, and Eric Mintz for their friendship and support over the years. I also acknowledge NIH grant NS 10596, the North American Association for the Study of Obesity (NAASO) and Indiana University for financial support.
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