Inflammation, Self-Regulation, and Health: An Immunologic Model of Self-Regulatory Failure

Abstract

Self-regulation is a fundamental human process that refers to multiple complex methods by which individuals pursue goals in the face of distractions. Whereas superior self-regulation predicts better academic achievement, relationship quality, financial and career success, and lifespan health, poor self-regulation increases a person's risk for negative outcomes in each of these domains and can ultimately presage early mortality. Given its centrality to understanding the human condition, a large body of research has examined cognitive, emotional, and behavioral aspects of self-regulation. In contrast, relatively little attention has been paid to specific biologic processes that may underlie self-regulation. We address this latter issue in the present review by examining the growing body of research showing that components of the immune system involved in inflammation can alter neural, cognitive, and motivational processes that lead to impaired self-regulation and poor health. Based on these findings, we propose an integrated, multilevel model that describes how inflammation may cause widespread biobehavioral alterations that promote self-regulatory failure. This immunologic model of self-regulatory failure has implications for understanding how biological and behavioral factors interact to influence self-regulation. The model also suggests new ways of reducing disease risk and enhancing human potential by targeting inflammatory processes that affect self-regulation.

Keywords: behavior; cognition; cytokines; development; disease; executive function; health; motivation; self-regulation.

Figure 1

Processes involved in self-regulation, arranged by their proximity to individual self-regulatory acts. Acts of self-regulation depend most proximally on the strength of an impulse, emotion, or reward, which both influence and are influenced by executive control abilities. This interplay is influenced by a person’s motivation to self-regulate, as motivation to self-regulate is crucial if sustained executive control is needed. Motivation is then in turn influenced by self-regulatory resources, as motivation to self-regulate will be low if one knows self-regulation is ultimately a futile effort. Self-regulatory resources are in turn affected by stress, as stress reduces self-regulatory resources. Finally, and most distally, beliefs and self-regulatory strategies can have an influential impact on self-regulation, due in part to how these factors may alter perceptions of both stress and self-regulatory resources.

Figure 2

Immunologic model of self-regulatory failure. Activation of the immune system is hypothesized to induce biological changes that alter neurocognitive and other biological processes that underpin self-regulation, leading to decrements in self-regulation. In particular, after a social-environmental stressor is neurally detected, the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes increase in activity, leading to a decrease in natural killer (NK) cell and helper T cell activity, and an increase in the release of numerous proinflammatory cytokines from immune cells. These immunologic dynamics then directly and indirectly influence neuronal activity, contributing to structural and functional changes in brain regions that support self-regulation. These neural alterations in turn produce an impaired self-regulatory phenotype, which leads to a decreased ability to successfully navigate stressful situations, ultimately increasing the likelihood of experiencing more stress in the future.

Figure 3

Immunologic model of self-regulatory failure from a developmental perspective. Exposure to stress, infection, and disease in early life increases proinflammatory cytokine activity, which decreases an individual’s self-regulatory ability. Poor self-regulation can in turn feedback to cause stress generation behaviors (e.g., saying a hurtful thing to a friend or loved one during an argument, not arriving on time to work) and poor health behaviors (e.g., not completing a course of antibiotics, not washing one’s hands), which lead to greater exposure to stress and disease. As these dynamics continue over childhood and adolescence, more stable differences in brain structure and function can develop that ultimately produce persistent impairments in self-regulation in adulthood.