Reflex control of immunity

Abstract

During sterile injury or infection, the innate immune system produces cytokines as part of the innate immune response. Molecules such as the cytokines tumour necrosis factor and interleukin-1 as well as high-mobility group box 1 protein are inherently toxic and can directly mediate the development of fever, shock, tissue injury, organ failure and even death. Visceral reflexes provide physiological homeostasis to complex organ systems (for example, the baroreflex in the cardiovascular system), and these principles also operate in the control of innate immune responses. The inflammatory reflex, a prototypical neural mechanism that modulates the immune system, consists of an afferent sensory arm that is activated by the products of sterile or infectious inflammation, and a motor arm, termed the cholinergic anti-inflammatory pathway, that inhibits pro-inflammatory cytokine release by the innate immune system. The molecular mechanism of cytokine regulation by the inflammatory reflex depends on signal transduction by the nicotinic acetylcholine receptor α7 subunit (α7nAChR). Administration of selective α7nAChR agonists or electrical stimulation of the inflammatory reflex inhibits pro-inflammatory cytokine release and confers protection against tissue damage. The immune system is not autonomous because immune responses are influenced by the inflammatory reflex. The inflammatory reflex maintains immune homeostasis as a set point function that influences the progression of inflammatory diseases.