Inhibition of phytohemagglutinin-induced lymphocyte proliferation by dexamethasone: Mechanisms of individual susceptibility

Pukhalsky, Alexander; Калашникова, Е. А.; Lyashko, V. N.; Pevnitsky, L.A.

doi:10.1016/0192-0561(90)90103-t

Cited by 14 publications

(7 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 H]thymidine incorporation in its absence (37), raising the possibility that the greater sensitivity in the injured was secondary to their lower proliferative response to ConA. However, we found no such relationship in either the patients or the control subjects.…”

Section: Discussioncontrasting

confidence: 55%

Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone

Rijen¹,

Harvey²,

Barton³

et al. 1998

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Elderly women with proximal femur fracture show a prolonged increase in plasma cortisol, which could have undesirable catabolic effects. Suppression of cortisol by dexamethasone is impaired, suggesting resistance to glucocorticoid effects at feedback inhibitory sites. We therefore wished to find out whether peripheral glucocorticoid sensitivity is normal. Design: Peripheral blood mononuclear leucocytes were used as a model tissue. Blood samples were taken from elderly women about 2 weeks after hip fracture and from elderly control women. Each patient was then given 1 mg dexamethasone at 2300 h followed by further sampling at 0800 and 1600 h the next day. Methods: Glucocorticoid-receptor binding parameters were measured by incubating whole cells with 3 H]thymidine than the control cells in the absence of dexamethasone. The percentage inhibition by a saturating concentration of dexamethasone was unchanged but the concentration giving half-maximal inhibition was decreased (sensitivity was increased) at the higher of the two concanavalin A concentrations used. Conclusions: These experiments in mononuclear leucocytes give no evidence of peripheral resistance to glucocorticoids in hip-fracture patients with impaired suppression of cortisol by dexamethasone. European Journal of Endocrinology 138 659-666

show abstract

Section: Discussioncontrasting

confidence: 55%

Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone

Rijen¹,

Harvey²,

Barton³

et al. 1998

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Pre viously the dire ct positive corre lation be tw een the le ve l of PHA-induc ed lymphoc yte prolife ratio n and of the inhibitio n de gree of such stimulation by dex amethasone (ED 50 ) has be en show n. On the basis of this c orre lation w e propose d the method of e valuation of individual susc eptibility to the antip roliferative effe ct of glucocortic oids by D h -parameter calculation. 14 D h w as calc ulate d using formula:…”

Section: Inhibition Of Pha-induced Lymphocyte Proliferation By Dexamementioning

confidence: 99%

Inflammatory Markers in Cystic Fibrosis Patients with Lung Pseudomonas aeruginosa Infection

Pukhalsky

Капранов

Калашникова

et al. 1999

Mediators of Inflammation

View full text Add to dashboard Cite

Chronic endobronchial inflammation and bacterial infection are the main causes of morbidity and mortality in cystic fibrosis (CF), an autosomal recessive genetic disorder associated with improper function of chloride channels. Inflammation in CF lung is greatly amplified after Pseudomonas aeruginosa infection. In this study the relationship between P. aeruginosa status and inflammatory markers has been investigated. Seventeen CF children in acute lung exacerbation were examined. CF patients without P. aeruginosa infection were characterized by elevated activity of sputum elastase, reduced response of peripheral blood lymphocytes to PHA and significant resistance to the antiproliferative action of glucocorticoids. These parameters were normalized after antibiotic treatment. The patients with prolonged P. aeruginosa infection demonstrated extremely high levels of elastase activity and elevated amounts of sputum IL-8 and TNF-alpha. Although antibiotic treatment resulted in clinical improvement, it failed to suppress excessive immune response in the lung. The data indicate that CF patients with prolonged P. aeruginosa need the modified treatment, which should include immunomodulating drugs and protease inhibitors as well as antibacterial therapy.

show abstract

“…The actual state of in vivo inhibition of lymphocyte activation in these patients is probably reflected by the significant decrease of circulat ing sIL-2R levels. The lack of significance in mitogeninduced DNA synthesis between all study groups may be due to the high interindividual variability intrinsic to the assay system [35], Whereas inhibitory effects of GCs on IL-2 production, IL-2R expression and DNA synthesis have been shown following exogenous administration of GCs or in in vitro settings [10][11][12]36], we provide evi dence that endogenous hypercortisolism results in an in vivo inhibition of the IL-2 system. As the interaction of IL 2 and its receptor has been shown to be essential for the development of a normal immune response [ 1,2], its inhi bition could be crucially involved in the clinically wellknown increased susceptibility of patients with Cushing's syndrome to infectious diseases.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of lnterleukin-2-Mediated Lymphocyte Activation in Patients with Cushing’s Syndrome: A Comparison with Hypocortisolemic Patients

Sauer

Stalla

Müller³

et al. 1994

Neuroendocrinology

View full text Add to dashboard Cite

We investigated the lymphocyte interleukin-2 (IL-2) system, which is critically involved in lymphocyte activation, in patients with disorders or the hypothalamic-pituitary-adrenal (HPA) axis. Patients with Cushing’s syndrome (n = 9) showed a significant (p < 0.05) inhibition of phytohemagglutinin (PHA)-stimulated IL-2 secretion by peripheral lymphocytes and a decrease of sensitivity to cortisol inhibition in vitro compared to normal subjects (n = 9). Circulating soluble interleukin-2 receptor (sIL-2R) levels were significantly decreased (p < 0.05), whereas no significant difference was observed in PHA-induced sIL-2R release in vitro. In patients with hypocortisolism (n = 12), in vitro IL-2 synthesis was increased compared to normal subjects and to patients with Cushing’s syndrome (p < 0.01). In vitro sIL-2R release was significantly higher (p < 0.01) compared to patients with Cushing’s syndrome. In contrast to patients with secondary adrenal insufficiency (n = 7), patients with an adrenal origin of hypocortisolism (Addison’s disease, bilateral adrenalectomy; n = 5) showed significantly elevated circulating sIL-2R levels compared to normal subjects and patients with Cushing’s syndrome (p < 0.005). There was no significant difference between the study groups in mitogen-induced DNA synthesis. This is the first description of alterations of cytokine secretion in patients with HPA axis disorders. The contrary effects of long-term hypercortisolism and insufficient or absent adrenal glucocorticoid secretion on IL-2-mediated lymphocyte activation could account for the immune states previously observed in these patients.

show abstract

Inhibition of phytohemagglutinin-induced lymphocyte proliferation by dexamethasone: Mechanisms of individual susceptibility

Cited by 14 publications

References 8 publications

Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone

Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone

Inflammatory Markers in Cystic Fibrosis Patients with Lung Pseudomonas aeruginosa Infection

Inhibition of lnterleukin-2-Mediated Lymphocyte Activation in Patients with Cushing’s Syndrome: A Comparison with Hypocortisolemic Patients

Contact Info

Product

Resources

About