Journal of Allergy and Clinical Immunology
III. Therapeutic and clinical implications of systemic allergic inflammationStress, chronic inflammation, and emotional and physical well-being: Concurrent effects and chronic sequelae☆,☆☆
Section snippets
Organization of the stress system
The HPA axis and the SNS are peripheral limbs of the stress system, whose main function is to maintain basal and stress-related homeostasis.1, 2 The central components of this system are located in the hypothalamus and the brain stem (Fig 1).2
The immune response and the inflammatory reaction
Any immune response, first, involves the recognition of a pathogen and, second, the mounting of a reaction against it. Broadly speaking, the different types of immune response fall into 2 categories: the innate (nonspecific) and the adaptive (specific) immune responses.6 Phagocytic cells (such as dendritic cells, monocytes, macrophages, and polymorphonuclear neutrophils) bind to microorganisms, internalize them, and kill them. Because phagocytic cells use primitive, nonspecific recognition
Adrenocortical hormones
The anti-inflammatory and immunosuppressive properties of glucocorticoids exerted through their ubiquitous intracellular receptors make them invaluable therapeutic agents in numerous diseases.7 The glucocorticoid receptor is a 777-amino-acid cytoplasmic protein with 3 major functional domains and several subdomains. The carboxyterminal region binds glucocorticoid, and the middle portion domain binds to specific sequences of DNA in the regulatory regions of glucocorticoid-responsive genes
Effects of the immune and inflammatory reaction on the HPA axis and the SNS
The last 2 to 3 decades provided evidence that, during an immune response, certain cytokines can signal the CNS, which, through a complex CRH-dependent pathway triggers the activation of both the HPA axis and the SNS.2 Most of the HPA axis-stimulating activity in plasma comes from 3 cytokines (TNF-α, IL-1, and IL-6), which are produced at inflammatory sites and elsewhere in response to inflammation. In most situations, TNF-α appears first, followed by simultaneous secretion of IL-1 and IL-6.
Defects of the HPA axis and/or SNS
Disturbances in the feedback between the HPA axis and the immune and inflammatory reaction have been observed in animals and humans (Table III).2An excessive HPA response to inflammation can mimic the stress or hypercortisolemic state, increase susceptibility to certain infectious agents and tumors, and increase resistance to autoimmune or inflammatory disease. Conversely, a defective HPA-axis response can mimic the glucocorticoid-deficient state and cause resistance to infections and neoplasms
Systemic inflammation and well-being
Like the stress response, the inflammatory reaction of an individual is crucial for survival of self and species.1, 2 Also like the stress response, inflammation is meant to be tailored to the stimulus and be time limited. A fully fledged systemic inflammatory reaction consists of activation of immune and immune accessory cells and resultant stimulation of 2 major programs: (1) the sickness syndrome and (2) the classic stress syndrome. As a result, the acute phase reaction and the pain program,
Therapeutic perspectives
Glucocorticoids and analogue agents that potentiate their actions are options for the treatment of autoimmune inflammatory diseases. By potentiating the secretion or the effects of hypothalamic CRH with CRH secretagogues, CRH agonists or CRH binding protein antagonists that cross the blood-brain barrier, the development of inflammatory disease in susceptible persons with a hypofunctional HPA axis may be prevented and, at the same time, correct CNS symptoms of CRH deficiency. Such an action
References (26)
- et al.
Stress Hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease
Trends Endocrinol Metab
(1999) - et al.
The concepts of stress and stress system disorders: overview of physical and behavioral homeostasis
JAMA
(1992) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation
N Engl J Med
(1995)- et al.
Corticosteroid therapy, nonendocrine disease, and corticosteroid withdrawal
Ultradian, circadian, and stress-related hypothalamic-pituitary-adrenal axis activity–a dynamic digital-to-analog modulation
Endocrinology
(1998)The stress response and immune function: clinical implications
NY Acad Sci
(2000)- et al.
Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids
Endocr Rev
(1996) - et al.
Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications
Proc Assn Am Phys
(1996) - et al.
Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects
Endocrinology
(1998) - et al.
Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors
J Immunol
(1998)
The pathophysiologic roles of interleukin-6 in human disease
Ann Intern Med
Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis
J Clin Endocrinol Metab
The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor
J Exp Med
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Dr. Chrousos is a Consultant Endocrinologist.
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Reprint requests: George P. Chrousos, MD, NICHD, NIH, Bldg 10/9D42, Bethesda, MD 20892-1583.