The glucocorticoid sensitivity of lymphocytes changes according to the activity of the hypothalamic-pituitary-adrenocortical system

Sauer, Joachim; Polack, Edith; Wikinski, Silvia; Holsboer, Florian; Stalla, Günter; Arzt, Eduardo

doi:10.1016/0306-4530(94)00058-i

Cited by 25 publications

(22 citation statements)

References 49 publications

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“…In fact, we did find that in active disease, total leukocyte and neutrophil counts were higher and lymphocytes were lower than that observed in matched controls. We observed that total white blood cell counts in each individual blood sample also affected TL, and CS patients had higher total leukocyte counts compared with healthy controls, similar to other series (21). However, after adjustment for total leukocyte count (as a covariate), no differences in TL between CS and their healthy controls were identified.…”

Section: European Journal Of Endocrinologysupporting

confidence: 54%

“…In addition, TL may be affected by what is known as a 'pseudolengthening' mechanism (20); specifically, TL of lymphocytes becomes increasingly shorter than those of granulocytes over the years (17). And as a redistribution of leukocyte cell type is often seen in hypercortisolism (lymphopenia and neutrophilia), this may also affect the measured TL obtained from the total leukocyte count (21). In fact, we did find that in active disease, total leukocyte and neutrophil counts were higher and lymphocytes were lower than that observed in matched controls.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

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Telomere length analysis in Cushing's syndrome

Aulinas

Ramírez

Barahona

et al. 2014

European Journal of Endocrinology

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Introduction: Hypercortisolism in Cushing's syndrome (CS) is associated with increased morbidity and mortality. Hypercortisolism also occurs in chronic depressive disorders and stress, where telomere length (TL) is shorter than in controls. We hypothesized that shortening of telomere might occur in CS and contribute to premature aging and morbidity. Aim: To investigate TL in CS patients compared with controls. Methods: Seventy-seven CS patients (14 males, 59 pituitary, 17 adrenal, and one ectopic; 21 with active disease) were compared with 77 gender-, age-, and smoking-matched controls. Fifteen CS were evaluated longitudinally, during active disease and after remission of hypercortisolism. Leukocyte TL was measured by telomere restriction fragment-Southern technique. Clinical markers were included in a multiple linear regression analysis to investigate potential predictors of TL. Results: Mean TL in CS patients and controls was similar (7667 vs 7483 bp, NS). After adjustment for age, in the longitudinal evaluation, TL was shorter in active disease than after remission (7273 vs 7870, P!0.05). Age and dyslipidemia were negative predictors (P!0.05), and total leukocyte count was a positive predictor for TL (P!0.05). As expected, a negative correlation was found between TL and age (CS, RZK0.400 and controls, RZK0.292; P!0.05). No correlation was found between circulating cortisol, duration of exposure to hypercortisolism or biochemical cure and TL. Conclusion: Even though in the cross-sectional comparison of CS and controls no difference in TL was found, in the longitudinal evaluation, patients with active CS had shorter TL than after biochemical cure of hypercortisolism. These preliminary results suggest that hypercortisolism might negatively impact telomere maintenance. Larger studies are needed to confirm these findings.

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Section: European Journal Of Endocrinologysupporting

confidence: 54%

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Telomere length analysis in Cushing's syndrome

Aulinas

Ramírez

Barahona

et al. 2014

European Journal of Endocrinology

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“…To our knowledge, this is the first study to demonstrate that a short-term psychosocial stress may induce cortisol resistance in PBMC cultures from neonates. Similarly, GC resistance of blood immune cells has been reported after a single physical exercise (3) or mental stress in humans (4,12,13). However, most previous work using socially defeated mice has shown decreased GC sensitivity of spleen cells, which was more pronounced in animals with higher number of injuries because of fighting (8,9).…”

Section: Discussionmentioning

confidence: 76%

“…Similarly, in academically stressed students, there was a positive correlation between the degree of lymphocyte activation and cortisol inhibition in vitro (12). It has been suggested that GC sensitivity of lymphocytes varies with the state of immunological activation of the cells and can be modulated by the GR number or expression level in the cells (33) and by the hormone binding affinity of the GR (4).…”

Section: Discussionmentioning

confidence: 99%

“…In students, it has been demonstrated that stress associated with academic examinations provokes an activation of the HPA axis with increased levels of cortisol followed by a transient decrease in the GC sensitivity of leukocytes ex vivo (12). Similarly, the laboratory Trier Social Stress Test induced changes in GC sensitivity for proinflammatory cytokine production by lipopolysaccharide (LPS)-stimulated whole blood cultures of healthy humans (4,13).…”

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confidence: 99%

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Altered Immunomodulation by Glucocorticoids in Neonatal Pigs Exposed to a Psychosocial Stressor

et al. 2010

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Stressful early life experiences can have short-and long-term effects on neuroendocrine and immune mechanisms of adaptation, which are primarily modulated by glucocorticoids. This study aimed to examine how the stress and immune systems interact to cope with psychosocial stress induced by a single social isolation (4 h) in neonatal pigs at 7, 21, or 35 d of age. This social isolation provoked increased plasma ACTH and cortisol concentrations and reduced TNF-␣ levels but had no significant effect on IL-6 levels. Socially isolated piglets had a higher lipopolysaccharide (LPS)-stimulated proliferative response of peripheral blood mononuclear cells (PBMCs) than controls, whereas concanavalin A (ConA)-induced proliferation was not affected by isolation. A single social isolation also induced a dose-dependent cortisol resistance in ConA-and LPS-stimulated PBMCs compared with controls, which may be an adaptive response in the short term. Moreover, LPS-stimulated cultures from control piglets showed a reduction in cortisol sensitivity with increasing age. Conclusively, these findings provide stress-related measures for the psychophysiological assessment of livestock handling practices but might also have implications for stress and health studies in young animals and humans. (Pediatr Res 68: 473-478, 2010)

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Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients

Mundy-Bosse

Thornton

Yang

et al. 2011

Cellular Immunology

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Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stage II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 µg/dl vs. 9.74 µg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/mL vs. 97.16 pg/mL; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, versus 27.3% in patients with low IES scores. Additional analyses of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = .064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients.

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The glucocorticoid sensitivity of lymphocytes changes according to the activity of the hypothalamic-pituitary-adrenocortical system

Cited by 25 publications

References 49 publications

Telomere length analysis in Cushing's syndrome

Telomere length analysis in Cushing's syndrome

Altered Immunomodulation by Glucocorticoids in Neonatal Pigs Exposed to a Psychosocial Stressor

Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients

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