Nervous and Immune System Interactions


Several mechanisms by which the nervous and immune systems might interact have now been recognized. The nervous system may affect immune function via direct innervation of immune organs and by secretion of hormones from the pituitary and other endocrine organs. Conversely, cells of the immune system may influence nervous system function by secretion of a variety of chemical messengers, among which cytokines are the best recognized. Also, although classically the brain was considered ‘immunologically privileged’, it is now recognized that cells of the immune system may be active in the brain, and that this may be an important factor in many central nervous system (CNS) diseases.

Keywords: immune system; nervous system; conditioning; stress; HPA axis; ACTH; CRF; corticosteroid; cytokines; behaviour; noradrenaline; serotonin; tryptophan

Figure 1.

Diagram of the interactions between the brain and components of the endocrine and immune systems. The ability of the brain to alter immune system function via a variety of endocrine pathways and the autonomic nervous system is emphasized, and the effects of peptides and cytokines produced by the immune system on immune cells and the brain is indicated. A, adrenaline (epinephrine); ACTH, adrenocorticotrophic hormone; CRF, corticotrophin‐releasing factor; CS, ; Enk, ; GH, ; NA, noradrenaline (norepinephrine); NPY, Y; SP, P; TNFα, . Modified from Dunn (1995).

Figure 2.

Diagram of the relationship of the brain, the hypothalamic–pituitary–adrenocortical (HPA) axis and immune cells. Interleukin‐1 (IL‐1), and possibly other cytokines, produced by lymphocytes during the immune response activates noradrenergic (NA) projections from the brainstem to the hypothalamic (PVN). This input activates the HPA axis, stimulating the release of corticotrophin‐releasing factor (CRF) from the median eminence of the hypothalamus. CRF stimulates the secretion of adrenocorticotrophic hormone (ACTH) from the anterior lobe of the pituitary, which in turn activates the adrenal cortex to synthesize and secrete glucocorticoid hormones. The glucocorticoids may provide a negative feedback on cytokine production by lymphocytes. Modified from Dunn (1995).


Further Reading

Ader R and Cohen N (1985) CNS–immune system interactions: conditioning phenomena. Behavioral and Brain Sciences 8: 379–426.

Ader R, Felten DL and Cohen N (2001) Psychoneuroimmunology, 3rd edn, pp. 649–666. San Diego, CA: Academic Press.

Besedovsky HO and del Rey A (1996) Immune‐neuro‐endocrine interactions: facts and hypotheses. Endocrine Reviews 18: 64–102.

Dantzer R, Wollman EE and Yirmiya R (1999) Cytokines, Stress, and Depression. Advances in Experimental Medicine and Biology. Vol 461, New York: Kluwer Academic/Plenum Publishers.

Dunn AJ (1995) Interactions between the nervous system and the immune system: implications for psychopharmacology. In: Bloom FE and Kupfer DJ (eds) Psychopharmacology: The Fourth Generation of Progress, pp. 719–731. New York: Raven Press.

Glaser R and Kiecolt‐Glaser J (1994) Handbook of Human Stress and Immunity. San Diego, CA: Academic Press.

Hart BL (1988) Biological basis of the behavior of sick animals. Neuroscience and Biobehavioral Reviews 12: 123–137.

Kent S, Bluthé R‐M, Kelley KW and Dantzer R (1992) Sickness behavior as a new target for drug development. Trends in Pharmacological Sciences 13: 24–28.

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Dunn, Adrian J(Sep 2005) Nervous and Immune System Interactions. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0004068]