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Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones
Abstract
The numbers and proportions of leukocytes in the blood provide an important representation of the state of activation of the immune system, and of the pattern of distribution of immune cells in the body. We have shown previously that acute stress induces large, rapid, and reversible changes in the distribution of peripheral blood leukocyte subpopulations in the rat. The studies described here specifically investigate the role played by adrenal steroid hormones in mediating stress-induced changes in blood leukocyte distribution. Since adrenal steroids act at two distinct receptor subtypes that show a heterogeneity of expression in immune cells and tissues, the role played by each subtype in mediating changes in leukocyte distribution is also investigated. Cyanoketone, a corticosterone (CORT) synthesis inhibitor, significantly reduced the decrease in lymphocyte numbers observed during stress and significantly enhanced the increase in neutrophil numbers observed after the cessation of stress. Acute administration of aldosterone (a specific type I adrenal steroid receptor agonist) to adrenalectomized animals did not have a significant effect on blood leukocyte numbers. In contrast, acute administration of CORT (the endogenous type I and type II receptor agonist), or RU28362 (a specific type II receptor agonist), to adrenalectomized animals produced changes in leukocyte distribution that were similar to those observed in intact animals during stress. These results suggest that CORT, acting at the type II adrenal steroid receptor, is a major mediator of the stress-induced changes in blood lymphocyte and monocyte distribution.
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“Greater levels of glucocorticoid are associated with higher numbers of circulating neutrophils, lower numbers of circulating lymphocytes, and a lower neutrophil-to-lymphocyte (N/L) ratio-an overall marker of the trafficking of these cells (e.g., refs.22,23).”
From Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk (2012) · cites this paper as [23]
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Lymphocyte subset numbers depend on the bacterial origin of sepsis
Holub, M., Klučková, Z., Helcl, M., PříAhodov, J., Rokyta, R., & Beran, O. (2003) · Clinical Microbiology and Infection · doi:10.1046/j.1469-0691.2003.00518.x · Cited by 86
Effects of hand massage on anxiety in cataract surgery using local anesthesia
Kim, M. S., Cho, K. S., Woo, H., et al. (2001) · Journal of Cataract & Refractive Surgery · doi:10.1016/s0886-3350(00)00730-6 · Cited by 90
Turner, J. E., Aldred, S., Witard, O. C., Drayson, M. T., Moss, P. M., & Bosch, J. A. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.07.239 · Cited by 90
“However, both animal and human evidence provide only limited support for this idea (Dhabhar et al., 1995, 1996).”
Does habitat fragmentation cause stress in the agile antechinus? A haematological approach
Johnstone, C. P., Lill, A., & Reina, R. D. (2011) · Journal of Comparative Physiology B · doi:10.1007/s00360-011-0598-7 · Cited by 83
“We suggest that it is unlikely that the N:L ratio represented an attenuated acute stress response in the pseudofragment males stemming from chronic stress in the undisturbed forest sites (Fig. 3) (Dhabhar and McEwen 1997; Dhabhar et al. 1996 ).”
BackgroundSmall, B. C., & Bilodeau, A. L. (2005) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2004.12.004 · Cited by 83
Physiology in conservation translocations
Tarszisz, E., Dickman, C. R., & Munn, A. J. (2014) · Conservation Physiology · doi:10.1093/conphys/cou054 · Cited by 83
“Additionally, persistent endocrinological responses to stressors can dampen the immune systems of animals, depressing their abilities to respond to immune challenges (Dhabhar et al., 1996), such as injury or exposure to pathogens or parasites (Bortolotti et al., 2009).”
BackgroundZhang, D., Kishihara, K., Wang, B., Mizobe, K., Kubo, C., & Nomoto, K. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00197-0 · Cited by 75
Hagenaars, A., Meyer, I. J., Herzke, D., Pardo, B. G., Martinez, P., Pabon, M., De Coen, W., & Knapen, D. (2011) · Aquatic Toxicology · doi:10.1016/j.aquatox.2011.04.012 · Cited by 74
Rosenberger, P. H., Ickovics, J. R., Epel, E. S., Nadler, E., Jokl, P., Fulkerson, J. P., Tillie, J. M., & Dhabhar, F. S. (2009) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.h.00989 · Cited by 76
Self-citationCole, S. W., Mendoza, S. P., & Capitanio, J. P. (2009) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181aa95a9 · Cited by 74
“Because this process is mediated specifically by GR signaling (42,47), the strength of association between circulating cortisol levels and leukocyte subset redistribution in circulating blood provides an in vivo hematological measure of immune cell sensitivity to regulation by endogenous glucocorticoids (30).”
BackgroundEffect of repeated restraint stress on the levels of intestinal IgA in mice
Jarillo‐Luna, A., Rivera‐Aguilar, V., Reyna-Garfias, H., Lara‐Padilla, E., Kormanovski, A., & Campos-Rodrı́guez, R. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.04.009 · Cited by 74
“Since glucocorticoids induce a redistribution of lymphocytes in several tissues (Dhabhar et al., 1995; Dhabhar et al., 1996; Dhabhar, 2002), they may reduce the homing of primed B-IgA+ cells to the mucosa.”
BackgroundNakamura, A., Fujiwara, S., Matsumoto, I., & Abe, K. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf900420g · Cited by 72
Smyth, G. P., Stapleton, P. P., Freeman, T. A., Concannon, E. M., Mestre, J. R., Duff, M., Maddali, S., & Daly, J. M. (2004) · Journal of Surgical Research · doi:10.1016/s0022-4804(03)00300-7 · Cited by 72
Metadata
- Authors
- Dhabhar, F. S., Miller, A. H., McEwen, B. S., & Spencer, R. L.
- Affiliations
- Rockefeller University (US)
- University of Colorado Boulder (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-08
- Volume
- 157
- Issue
- 4
- Pages
- 1638-1644
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2127386463
- Cited by
- 480
- References
- 0
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 11 · 2023: 9 · 2022: 13 · 2021: 15 · 2020: 13 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 14 · 2015: 21 · 2014: 21 · 2013: 13 · 2012: 23
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- acute stress, adrenal steroids, corticosterone, type II glucocorticoid receptor, aldosterone, lymphocyte distribution, adrenalectomy, cyanoketone, immune activation
- MeSH terms
- Adrenal Cortex, Adrenal Cortex Hormones, Adrenalectomy, Aldosterone, Animals, Corticosterone, Cyanoketone, Enzyme Inhibitors, Leukocyte Count, Male, Receptors, Glucocorticoid, Restraint, Physical, Stress, Psychological, 3-Hydroxysteroid Dehydrogenases, Lymphocyte Subsets, Rats, Sprague-Dawley, Receptors, Mineralocorticoid, Rats
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