Neural Control of Inflammation: Bioelectronic Medicine in Treatment of Chronic Inflammatory Disease

Inflammation is important for antimicrobial defense and for tissue repair after trauma. The inflammatory response and its resolution are both active processes that must be tightly regulated to maintain homeostasis. Excessive inflammation and nonresolving inflammation cause tissue damage and chronic disease, including autoinflammatory and cardiovascular diseases. An improved understanding of the cellular and molecular mechanisms that regulate inflammation has supported development of novel therapies for several inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease. Many of the specific anticytokine therapies carry a risk for excessive immunosuppression and serious side effects. The discovery of the inflammatory reflex and the increasingly detailed understanding of the molecular interactions between homeostatic neural reflexes and the immune system have laid the foundation for bioelectronic medicine in the field of inflammatory diseases. Neural interfaces and nerve stimulators are now being tested in human clinical trials and may, as the technology develops further, have advantages over conventional drugs in terms of better compliance, continuously adaptable control of dosing, better monitoring, and reduced risks for unwanted side effects. Here, we review the current mechanistic understanding of common autoinflammatory conditions, consider available therapies, and discuss the potential use of increasingly capable devices in the treatment of inflammatory disease.