Reciprocal regulation of the neural and innate immune systems

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Innate immune responses are regulated by microorganisms and cell death, as well as by a third class of stress signal from the nervous and endocrine systems. The innate immune system also feeds back, through the production of cytokines, to regulate the function of the central nervous system (CNS), and this has effects on behaviour. These signals provide an extrinsic regulatory circuit that links physiological, social and environmental conditions, as perceived by the CNS, with transcriptional 'decision-making' in leukocytes. CNS-mediated regulation of innate immune responses optimizes total organism fitness and provides new opportunities for therapeutic control of chronic infectious, inflammatory and neuropsychiatric diseases.

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Figure 1: CNS regulation of innate immune response gene programmes.
Figure 2: Multi-circuit control of the innate immune transcriptome.


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The authors are supported by grants R01-AG034588, R01-AG026364, R01-CA119159, R01-HL079955, P30-AG028748 and R01-MH091352 (to M.R.I.); grants R01-CA116778, R01-AG033590, R21-CA138687 and P30-AG028748 (to S.W.C.); and the Cousins Center for Psychoneuroimmunology.

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Correspondence to Michael R. Irwin.

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Belonging to the same species.


A class of steroid hormones that are involved in carbohydrate, protein and fat metabolism. These hormones are anti-inflammatory and immunosuppressive.


(HPA). This term refers to a complex set of direct influences and feedback interactions between the hypothalamus, the pituitary gland (a pea-shaped structure located below the hypothalamus) and the adrenal glands (small, conical organs on top of the kidneys).

Non-rapid eye movement sleep

(NREM sleep). The sleep stages 1–3 (previously known as stages 1–4) are collectively referred to as NREM sleep. Rapid eye movement (REM) sleep is not included. There are distinct electroencephalographic and other characteristics seen in each stage, and there is usually little or no eye movement during NREM sleep. Dreaming is rare during NREM sleep, and muscles are not paralyzed as in REM sleep.

Social ecology

A broad range of complex physical and symbolic features of the environment that are created by the presence of conspecifics (including social structures such as cultural systems or socio-economic status), as well as physical processes, such as transmission of communicable diseases, provision of medical care or physical aggression.

Sympathetic nervous system

(SNS). One of three parts of the autonomic nervous system (along with the enteric and parasympathetic systems). The SNS serves to mobilize the body's resources during flight-or-flight stress responses.

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Irwin, M., Cole, S. Reciprocal regulation of the neural and innate immune systems. Nat Rev Immunol 11, 625–632 (2011) doi:10.1038/nri3042

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