Effects of selective type I and II adrenal steroid agonists on immune cell distribution.
ABSTRACT Adrenal steroids exert their effects through two distinct adrenal steroid receptor subtypes; the high affinity type I, or mineralocorticoid, receptor and the lower affinity type II, or glucocorticoid, receptor. Adrenal steroids have well known effects on immune cell distribution, and although both type I and II receptors are expressed in immune cells and tissues, few data exist on the relative effects mediated through these two receptor subtypes. Accordingly, we administered selective type I and II adrenal steroid receptor agonists to young adult male Sprague-Dawley rats for 7 days and then measured immune cell distribution in the peripheral blood and spleen. Results were compared with those of similar studies using the naturally occurring glucocorticoid of the rat, corticosterone, which binds both type I and II receptors. The majority of the well characterized effects of adrenal steroids on peripheral blood immune cells (increased neutrophils and decreased lymphocytes and monocytes) were reproduced by the type II receptor agonist, RU28362. RU28362 decreased the numbers of all lymphocyte subsets [T-cells, B-cells, and natural killer (NK) cells] to very low absolute levels. The largest relative decrease (i.e. in percentage) was seen in B-cells, whereas NK cells exhibited the least relative decrease and actually showed a 2-fold increase in relative percentage during RU28362 treatment. Similar to RU28362, the type I receptor agonist, aldosterone, significantly reduced the number of lymphocytes and monocytes. In contrast to RU28362, however, aldosterone significantly decreased the number of neutrophils. Moreover, aldosterone decreased the number of T-helper cells and NK cells, while having no effect on the number of B-cells or T-suppressor/cytotoxic cells. Corticosterone at physiologically relevant concentrations had potent effects on immune cell distribution, which were indistinguishable from those of the type II receptor agonist, RU28362. Taken together, these results indicate that effects of adrenal steroids on immune cell distribution are dependent on the receptor subtype involved as well as the specific cell type targeted. These factors allow for varied and complex effects of adrenal steroids on the immune system under physiological conditions.
- SourceAvailable from: Gianluigi Mazzoccoli
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- "Besides, elderly subjects have decreased levels of CD20 þ cells (B lymphocytes), higher levels of CD25 þ cells (activated T lymphocytes with expression of the a chain of IL-2 receptor) and the circadian rhythmicity of these lymphocyte subsets is severely altered (Mazzoccoli et al., 2010b). The circadian system drives neuroendocrine secretion , and the hypothalamus-pituitary axis plays an immunomodulating role and influences cellular immune responses by releasing various hormones and neuropeptides with direct modulatory action on the immune effectors into the blood, or by regulating the hormonal secretion of peripheral endocrine glands (Besedovsky & del Rey, 1996; Dhabhar et al., 1995; Dimitrov et al., 2009; Kronfol et al., 1997; Mazzoccoli et al., 1997, 2010a; Miller et al., 1994; Ottaway & Husband, 1994; Petrovsky, 2001). The loss of circadian variation of CD4 þ T lymphocytes may consequently cause loss of timed window of interaction with the neuroendocrine hormones that play an immunomodulatory role: cortisol, melatonin, prolactin, thyrotropinreleasing hormone (TRH), thyroid-stimulating hormone (TSH), and the GH/insulin-like growth factor 1 (IGF1) axis (Arlt & Hewison, 2004). "
ABSTRACT: Various features, components, and functions of the immune system present daily variations. Immunocompetent cell counts and cytokine levels present variations according to the time of day and the sleep-wake cycle. Moreover, different immune cell types, such as macrophages, natural killer cells, and lymphocytes, contain a circadian molecular clockwork. The biological clocks intrinsic to immune cells and lymphoid organs, together with inputs from the central pacemaker of the suprachiasmatic nuclei via humoral and neural pathways, regulate the function of cells of the immune system, including their response to signals and their effector functions. Consequences of this include, for example, the daily variation in the response to an immune challenge (e.g., bacterial endotoxin injection) and the circadian control of allergic reactions. The circadian-immune connection is bidirectional, because in addition to this circadian control of immune functions, immune challenges and immune mediators (e.g., cytokines) were shown to have strong effects on circadian rhythms at the molecular, cellular, and behavioral levels. This tight crosstalk between the circadian and immune systems has wide-ranging implications for disease, as shown by the higher incidence of cancer and the exacerbation of autoimmune symptoms upon circadian disruption. (Author correspondence: email@example.com).Chronobiology International 05/2013; 30(7). DOI:10.3109/07420528.2013.782315 · 2.88 Impact Factor
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- "In information theory, a signal is the sequence of states in a communication channel that encodes a message and only analog and digital signals that are representations of analog physical quantities are considered as signals in the context of signal processing . The multiple components that constitute the neuroendocrine-immune system and the biological processes that characterize their function show patterns of rhythmic variation and multiple rhythms coexist presenting different phases   . "
ABSTRACT: Any quantity varying in the spatial-temporal dimension may be considered as a signal. Human lymphocyte cell surface molecules and subsets present circadian variation and this variation may represent a kind of signalling in the neuroendocrine-immune system. We have analyzed the dynamics of variation of specific lymphocyte subsets in healthy humans. In our study, lymphocyte subpopulation analyses were performed and cortisol, melatonin, GH and TSH serum levels were measured on blood samples collected every 4h for 24 hours from eleven healthy men, ages 35-53 years (mean=44±6SD). A clear circadian rhythm was validated for CD8 and cortisol with acrophase during the day and for CD3, CD4, melatonin, GH and TSH with acrophase at night. Cross-correlation showed that CD3 correlated positively with CD4 (ρ=0.67, P<0.05) and negatively with CD8 (ρ=-0.41, P<0.05), CD4 correlated positively with melatonin (ρ=0.90, P<0.05), GH (ρ=0.92, P<0.05) and TSH (ρ=0.71, P<0.05), negatively with CD8 (ρ=-0.90, P<0.05) and cortisol (ρ=-0.18, P<0.05), CD8 correlated positively with cortisol (ρ=0.38, P<0.05). The different profiles of nyctohemeral changes of lymphocyte cell surface molecules and specific lymphocyte subsets realize different relationships with the neuroendocrine hormones and might represent a way of signal transmission among the multiple components of the neuroendocrine-immune system.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 07/2011; 65(4):275-9. DOI:10.1016/j.biopha.2011.02.002 · 2.11 Impact Factor
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- "Stress is also a powerful stimulator of leukocytes redistribution in different species including the mouse and humans (Cohen, 1972; Dale et al., 1975; Dhabhar and McEwen, 1996, 1997; Dhabhar et al., 1994; Fauci, 1976; Fauci and Dale, 1974, 1975; McEwen et al., 1997; Miller et al., 1994; Onsrud and Thorsby, 1981; Spain and Thalhimer, 1951). This phenomenon is regarded as an adaptive response enhancing immune surveillance in compartments more likely to be exposed to infections (i.e. "
ABSTRACT: Inflammation and stress are regarded as two important atherogenic factors. Because stress can affect leukocyte distribution, we hypothesized that stress-mediated leukocyte extravasation can modify the inflammatory environment of the arterial wall possibly contributing to atherogenesis. To test this hypothesis we evaluated the inflammatory environment of the aorta in C57Bl/6 mice subjected to 3 and 12 months of chronic stress and compared it to age matched non-stressed animals. Experiments were carried out in mice fed regular chow or atherogenic diets. Both treatments increased the expression of vascular and leukocyte adhesion molecules and leukocyte accumulation. At 3 months, stress but not an atherogenic diet elevated the number of CD4 cells, CD8 cells, macrophages, dendritic cells and neutrophils. These changes were associated with elevation of transcripts for ICAM-1 and VCAM-1, E-selectin and neuropeptide Y. At 12 months, stress or high cholesterol acted similarly to elevate the number of CD8 and macrophages, and synergistically on the number of all cell types investigated. At this time-point, strong synergism was also observed on the level of E-selectin and NPY in the aorta, but not in the circulation. Despite these effects, histological and morphological alterations of the arterial wall were severe in the atherogenic diet, but not in the stress groups. Thus, although stress and an atherogenic diet may both affect leukocyte accumulation in the aorta, they may contribute differently to atherogenesis.Brain Behavior and Immunity 06/2011; 25(8):1649-57. DOI:10.1016/j.bbi.2011.06.007 · 6.13 Impact Factor