Trends in Immunology
How stress influences the immune response
Section snippets
HPA axis and glucocorticoid hormones
The hypothalamus receives and monitors information about the environment and coordinates responses through nerves and hormones. Visual information, smell, hearing, temperature sensation and pain alert the hypothalamus to emergencies or environmental hazards. The emotional portions of the brain also relay information to the hypothalamus. From this integrative center, the brain controls hormone secretion from the pituitary gland and other tissues, such as the adrenal glands. For example,
Mechanisms of action for GC hormones
Being lipophilic molecules, GC hormones readily pass through the plasma membrane of all cells in the body. If a cell possesses a GC receptor (GR), that cell can be a target for action. There are two receptors for GC hormones, the GR and the mineralocorticoid receptor (MR). Because corticosterone has a higher affinity for MR than for GR [24], at low circulating levels glucocorticoid hormones bind preferentially to MR. Only at high circulating or tissue levels (i.e. during stress) is the GR
Sympathetic nervous system, adrenal medulla and catecholamines
In addition to regulation of immune function by glucocorticoid hormones associated with distress, it is known that catecholamines also modulate a range of immune functions, including cell proliferation, cytokine and antibody production, cytolytic activity and cell trafficking (reviewed in Refs 1, 45, 46). Catecholamines often act in concert with activation of the HPA axis. For example, paralleling the increase of GC-hormone production from the adrenal cortex, activation of the HPA axis also
Mechanism of action for catecholamines
Catecholamines mediate their effect on target tissues through adrenergic receptors and numerous cells of the immune system, including lymphocytes and macrophages, express adrenoreceptors. These are G-protein coupled receptors that can be divided into two subgroups, the α- and β-adrenergic receptors. It appears that the most important receptor for the immune system is the β2-adrenergic receptor [46]. β-adrenergic receptors function as intermediaries in transmembrane signaling pathways that
Conclusions
This Review has focused on GC hormones and catecholamines as the two major mediators of the stress effects on immune responses. However, other physiologic pathways are undoubtedly involved in the interplay. For example, endogenous opioids have recently been shown to diminish NK-cell cytotoxicity. In addition, a neuropeptide, substance P, is able to reduce inflammatory responses by suppressing IL-16 production by eosinophils. Whereas the focus of the anti-inflammatory effects of GC center on
Acknowledgements
This research was supported in part by NIH grants P50 DE13749 and PO1 AG16321, MH42096 MERIT AWARD, NIH General Clinical Research Center Grant MO1-RR-0034, and Ohio State University Comprehensive Cancer Center Core Grant CA16058.
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