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The Stress Response and the Regulation of Inflammatory Disease
- Esther M. Sternberg, MD;
- George P. Chrousos, MD;
- Ronald L. Wilder, MD, PhD; and
- Philip W. Gold, MD
Abstract
▪ The molecular and biochemical bases for interactions between the immune and central nervous systems are described. Immune cytokines not only activate immune function but also recruit central stressresponsive neurotransmitter systems in the modulation of the immune response and in the activation of behaviors that may be adaptive during injury or inflammation. Peripherally generated cytokines, such as interleukin-1, signal hypothalamic corticotropin-releasing hormone (CRH) neurons to activate pituitary-adrenal counterregulation of inflammation through the potent anti-inflammatory effects of glucocorticoids.
Corticotropin-releasing hormone not only activates the pituitary-adrenal axis but also sets in motion a coordinated series of behavioral and physiologic responses, suggesting that the central nervous system may coordinate both behavioral and immunologic adaptation during stressful situations. The pathophysiologic perturbation of this feedback loop, through various mechanisms, results in the development of inflammatory syndromes, such as rheumatoid arthritis, and behavioral syndromes, such as depression.
Thus, diseases characterized by both inflammatory and emotional disturbances may derive from common alterations in specific central nervous system pathways (for example, the CRH system). In addition, disruptions of this communication by genetic, infectious, toxic, or pharmacologic means can influence the susceptibility to disorders associated with both behavioral and inflammatory components and potentially alter their natural history. These concepts suggest that neuropharmacology agents that stimulate hypothalamic CRH might potentially be adjunctive therapy for illnesses traditionally viewed as inflammatory or autoimmune.
Article and Author Information
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An edited summary of a Combined Clinical Staff Conference held 30 May 1990 at the National Institutes of Health, Bethesda, Maryland.
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of the reference:
Gold PW. The stress response, depression, and inflammatory disease, pp 861-864. In: Sternberg EM, moderator. The stress response and the regulation of inflammatory disease. Ann Intern Med. 1992;117:854-866.
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Requests for Reprints: Esther Sternberg, MD, National Institute of Mental Health, Building 10, Room 3S-231, 9000 Rockville Pike, Bethesda, MD 20892.
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Current Author Addresses: Drs. Sternberg and Gold: National Institute of Mental Health, Building 10, Room 3S231, Bethesda, MD 20892.
Dr. Chrousos: National Institute of Child Health and Development, Building 10, Room 10N262, Bethesda, MD 20892.
Dr. Wilder: National Institute of Arthritis, Musculoskeletal and Skin Diseases, Building 10, Room 9N228, Bethesda, MD 20892.
