A Return to Wisdom: Using Sickness Behaviors to Integrate Ecological and Translational Research

Abstract

Sickness is typically characterized by fever, anorexia, cachexia, and reductions in social, pleasurable, and sexual behaviors. These responses can be displayed at varying intensities both within and among individuals, and the adaptive nature of sickness responses can be demonstrated by the context-dependent nature of their expression. The study of sickness has become an important area of investigation for researchers in a wide range of areas, including psychoneuroimmunology (PNI) and ecoimmunology (EI). The general goal of PNI is to identify key interactions among the nervous, endocrine and immune systems and behavior, and how disruptions in these processes might contribute to disease states. EI, in turn, has been established more recently within the perspectives of ecology and evolutionary biology, and is aimed more at understanding natural variation in immune function and sickness responses within a broadly integrative, organismal, and evolutionary context. The goal of this review is to examine the literature on sickness from both basic and biomedical perspectives within PNI and EI and to demonstrate how the integrative study of sickness behavior can serve as an integrating agent to connect ecological and translational approaches to the study of disease. By focusing on a set of specific exemplars, including the energetics of sickness, social context, and environmental influences on sickness, we hope to accomplish the larger goal of developing a common synthetic framework to understand sickness from multiple levels of analysis and varying perspectives across the fields of PNI and EI. By applying this integrative approach to sickness, we will be able to develop a more comprehensive view of sickness as a suite of adaptive responses rather than the simply deleterious consequences of illness.

Fig. 1

Effects of adaptive versus pathological sickness responses on behavior. In normal individuals who become transiently infected with disease, the systemic infection triggers an acute phase response (APR) and the release of peripheral cytokines, which leads to concomitant changes in brain cytokine production. Proinflammatory cytokines coordinate a wide range of adaptive behaviors (e.g., sickness behaviors) that help fight infection, including reduced feeding, fever (or hypothermia), decreased activity/increased sleep and reduced social interactions. When sickness responses become chronic or excessive, however, they can lead to pathological conditions, which may include metabolic syndrome, neuroinflammation, fatigue, and increases in withdrawal and depression. These symptoms of chronic sickness are consistent with symptoms typically associated with a range of neuropsychiatric and affective disorders. Figure modified from Bilbo and Schwarz (2012)

Fig. 2

Graphical model representing the various internal physiological mechanisms and external factors regulating sickness behavior. Both psychoneuroimmunology (PNI) and ecoimmunology (EI) have provided unique yet complementary perspectives and methodologies to study sickness behavior, allowing researchers to develop a more comprehensive view of sickness as a suite of adaptive responses rather than deleterious consequences, though sickness behavior can be costly in and of itself. Sickness behavior (fever/hypothermia, anorexia, cachexia, reductions in social, pleasurable, and sexual behaviors) can be displayed at varying intensities, and the adaptive nature of sickness responses can be demonstrated by the context-dependent nature of their expression. Here, we present the varying internal physiological mechanisms regulating sickness behavior (e.g., leptin, glucocorticoids, insulin), alongside the environmental (e.g., daylight, temperature, soil composition) and social contexts (e.g., predators, mates, young) that modulate the expression of these behaviors to varying degrees as well. Individuals incorporate complex cues from many different abiotic and biotic factors to appropriately respond to immune challenge. The body must maintain a state of homeostasis by providing energy to the most essential systems in diverse energetic, social, and environmental contexts, and as researchers, we must integrate what we learn from all of these frameworks to understand the function and adaptive capacity of sickness behaviors.