Neural Immune Pathways and Their Connection to Inflammatory Diseases

Arthritis Res Ther. 2003;5(6):251-65. doi: 10.1186/ar1002. Epub 2003 Sep 23.


Inflammation and inflammatory responses are modulated by a bidirectional communication between the neuroendocrine and immune system. Many lines of research have established the numerous routes by which the immune system and the central nervous system (CNS) communicate. The CNS signals the immune system through hormonal pathways, including the hypothalamic-pituitary-adrenal axis and the hormones of the neuroendocrine stress response, and through neuronal pathways, including the autonomic nervous system. The hypothalamic-pituitary-gonadal axis and sex hormones also have an important immunoregulatory role. The immune system signals the CNS through immune mediators and cytokines that can cross the blood-brain barrier, or signal indirectly through the vagus nerve or second messengers. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. This review discusses neuroimmune interactions and evidence for the role of such neural immune regulation of inflammation, rather than a discussion of the individual inflammatory mediators, in rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / physiopathology
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / physiopathology
  • Arthritis, Rheumatoid / therapy
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / physiopathology
  • Autoimmune Diseases / therapy
  • Autonomic Nervous System / physiopathology
  • Cytokines / physiology
  • Disease Models, Animal
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology
  • Immune System / physiopathology*
  • Inflammation / immunology
  • Inflammation / physiopathology*
  • Inflammation Mediators / physiology
  • Mice
  • Mice, Mutant Strains
  • Neuroimmunomodulation / physiology*
  • Neurosecretory Systems / physiopathology*
  • Neurotransmitter Agents / physiology
  • Pituitary-Adrenal System / physiopathology
  • Rats
  • Rats, Inbred Strains
  • Second Messenger Systems / physiology
  • Vagus Nerve / physiopathology


  • Cytokines
  • Inflammation Mediators
  • Neurotransmitter Agents