Immune-to-brain signaling and substrates of altered behavior during inflammation

Abstract

During the systemic inflammatory response to acute infection, and when in a safe environment, endothermic mammals typically display reduced activity and food intake, increased sleep, and the adoption of a curled-up position. These changes in behavior, in concert with fever, are adaptive in that they contribute to host survival. The present review addresses the immune-to-brain signaling pathways as well as possible neural substrates mediating reduced exploration and food intake during acute systemic inflammation. These involve rapid activation of peripheral nerves and glutamatergic brainstem circuits as well as slower IL-1beta action in the brain activating limbic and possibly ventral hypothalamic structures. Although mostly adaptive acutely, behavioral changes during inflammation may also reflect brain dysfunction in severe sepsis-associated delirium or become maladaptive and result in depression due to medical conditions that involve long-term inflammatory episodes with pain or discomfort. The mechanisms underlying these conditions are presently ill-understood even though neuroinflammation and neurodegeneration occur during and subsequent to sepsis-associated brain dysfunction, respectively.Copyright © 2016 OAE Publishing Inc.