Free Cortisol Index: A Rapid and Simple Estimation of Free Cortisol in Human Plasma1

Baumann, Gerhard; Rappaport, Georges; Lemarchand-Béraud, T; Felber, J. P.

doi:10.1210/jcem-40-3-462

Cited by 47 publications

(14 citation statements)

References 12 publications

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“…These GC concentrations are clearly in the therapeutic range. On one hand, physiological plasma cortisol levels range from 8 to 220 ng/ml during the diurnal cycle (27) with a biologically available (14) concentration of free cortisol of 0.8-28 ng/ml (27). On the other hand, GC therapy results in sustained plasma drug levels of 1-2 gg/ml with as much as 100 to 500 ng unbound hormone (12,13).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon.

Schaffner¹

1985

J. Clin. Invest.

196

125

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By exposing human blood-derived macrophages and alveolar macrophages in vitro to dexamethasone, we showed in these studies that glucocorticoids markedly suppress the antimicrobial activity of macrophages but not macrophage activation by lymphokines. As little as 2.5 X 10-8 mol/liter of dexamethasone prevented macrophages from inhibiting germination of Aspergillus spores or from eliminating ingested bacteria such as Listeria, Nocardia, or Salmonella. Damage to macrophage function was inhibited by progesterone and appeared to be receptor-mediated. In accordance with in vivo observations, dexamethasone required 24-36 h to suppress antimicrobial activity. While glucocorticoids interfered with base-line activity of macrophages, dexamethasone concentrations comparable to drug levels in patients had no effect on macrophage activation. Proliferating lymphocytes and 'y-interferon thus increased the antimicrobial activity of phagocytes exposed to glucocorticoids over that of control cells. Macrophage activation and correction of the dexamethasone effect by 'y-interferon, however, was dependent on the pathogen. The lymphokine enhanced the antimicrobial activity of dexamethasone-treated macrophages against Listeia and Salmonella but not against Aspergillus or Nocardia. Dexamethasone-induced damage to the antimicrobial activity of human macrophages in vitro parallels observations that glucocorticoids render laboratory animals susceptible to listeriosis and aspergillosis by damaging resident macrophages. Suppression of macrophage antimicrobial activity should thus be considered when treating patients with glucocorticoids; its prevention byinterferon might be beneficial for some but not all pathogens.

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Section: Discussionmentioning

confidence: 99%

Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon.

Schaffner¹

1985

J. Clin. Invest.

196

125

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“…107 Indirect estimation of free serum cortisol As a practical alternative to direct measurement of free serum cortisol, methods for estimating the unbound fraction of cortisol based on the binding characteristics of CBG have been proposed. 110,111 Calculation of free cor tisol levels is less technically demanding than direct measurement and uses measurements of total serum cortisol and CBG, for which commercial assays are available. Furthermore, calculated free cortisol levels show good correlations with direct measurements of free serum cortisol concentrations.…”

Section: Extracellular Tissue Techniquesmentioning

confidence: 99%

Regulation of cortisol bioavailability—effects on hormone measurement and action

2012

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Routine assessment of the hypothalamic-pituitary-adrenal axis relies on the measurement of total serum cortisol levels. However, most cortisol in serum is bound to corticosteroid-binding globulin (CBG) and albumin, and changes in the structure or circulating levels of binding proteins markedly affect measured total serum cortisol levels. Furthermore, high-affinity binding to CBG is predicted to affect the availability of cortisol for the glucocorticoid receptor. CBG is a substrate for activated neutrophil elastase, which cleaves the binding protein and results in the release of cortisol at sites of inflammation, enhancing its tissue-specific anti-inflammatory effects. Further tissue-specific modulation of cortisol availability is conferred by corticosteroid 11β-dehydrogenase. Direct assessment of tissue levels of bioavailable cortisol is not clinically practicable and measurement of total serum cortisol levels is of limited value in clinical conditions that alter prereceptor glucocorticoid bioavailability. Bioavailable cortisol can, however, be measured indirectly at systemic, extracellular tissue and cell levels, using novel techniques that have provided new insight into the transport, metabolism and biological action of glucocorticoids. A more physiologically informative approach is, therefore, now possible in the assessment of the hypothalamic-pituitary-adrenal axis, which could prove useful in clinical practice.

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“…Normal total circulating levels of cortisol, bound and free, are from about 1 X 10" 7 M to 8 X 10" 7 M (132,133). Studies were carried out to determine whether corticosteroids in doses normally given to patients might have an inhibitory effect upon superoxide anion production.…”

Section: Corticosteroid-induced Changes In Phospholipid Membranesmentioning

confidence: 99%

Corticosteroid-Induced Changes in Phospholipid Membranes as Mediators of Their Action*

Nelson

1980

Endocrine Reviews

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T HIS SHORT review will describe mechanisms by which corticosteroid modification of cellular phospholipids and particularly the phospholipid-structure of a variety of membranes can produce some of the effects of the corticosteroids. In addition to these effects, many studies have demonstrated effects of other hormones to alter specific phospholipids, phospholipases, or for phospholipase action on cells to mimic hormone action. All actions of the corticosteroids are not thought to be produced by these lipid alterations, but such changes are capable of producing widespread effects on receptor activity, RNA and protein synthesis, enzymatic activity, and transport through membranes. The availability of new data indicating that phospholipids are altered considerably by corticosteroids in a number of tissues makes a review of this subject of interest at this time.Corticosteroids are secreted in response to a variety of "stresses" that represent alterations in the cellular environment that might result in death or injury to the exposed cells if proper adaptation did not occur. Thus, these hormones are increased in response to anoxia, very low or very high temperature, or hypoglycemia. Through mechanisms that have not been clearly understood the cell is protected by the increased hormones against potentially harmful alterations in its environment. Unicellular organisms, which lack a sophisticated endocrine system for response to stresses, undergo modifications in cellular membranes in response to stress. A decrease in the temperature at which the organism is grown would produce a decrease in the fluidity of the membrane with resulting marked effects upon membrane-bound enzymatic activities. Similarly, increased temperature would result in increased fluidity of the lipid membrane and similar alterations in its function. In order

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Free Cortisol Index: A Rapid and Simple Estimation of Free Cortisol in Human Plasma1

Cited by 47 publications

References 12 publications

Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon.

Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon.

Regulation of cortisol bioavailability—effects on hormone measurement and action

Corticosteroid-Induced Changes in Phospholipid Membranes as Mediators of Their Action*

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