Intact or “active” corticosteroid-binding globulin (CBG) and total CBG in plasma: Determination by parallel ELISAs using monoclonal antibodies

Lewis, John G.; Elder, Peter A.

doi:10.1016/j.cca.2012.11.016

Cited by 32 publications

(37 citation statements)

References 23 publications

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“…FC concentrations obtained with the different FC surrogate assays are not identical (our data and [17,29]). This may be due to combinations of factors: non-standardized analytical methods [17,29], partial cortisol metabolism by the 11β-hydroxysteroid dehydrogenase type 2 in the salivary glands [14], approximations of calculations and constants [19,20], ratio of intact versus cleaved but immunoreactive CBG [30], etc. However, cortisol concentrations reflecting free measured or calculated serum cortisol or salivary cortisol are linearly correlated as expected and previously reported [17,29].…”

Section: Discussionmentioning

confidence: 99%

Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing

Brossaud

Gatta

Tabarin

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Section: Discussionmentioning

confidence: 99%

Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing

Brossaud

Gatta

Tabarin

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Additionally, no significant correlations were evident between levels of cortisol and levels of NK cytotoxicity, at baseline or following these manipulations, despite marked variations in both indices [21]. One factor that might explain the protective effects of plasma and of the in vivo milieu against suppression of NKCC by glucocorticoids is the presence of corticosteroid-binding-globulins, which bind up to 90% of glucocorticoid molecules [47], reducing the effective concentrations of glucocorticoids, and potentially buffering their effects [16]. …”

Section: Discussionmentioning

confidence: 99%

The misleading nature of in vitro and ex vivo findings in studying the impact of stress hormones on NK cell cytotoxicity

Gotlieb

Rosenne

Matzner

et al. 2015

Brain, Behavior, and Immunity

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In vitro and ex-vivo studies assessing the impact of stress hormones on immune competence commonly replace the natural milieu of leukocytes with an artificial medium, excluding plasma factors, hormones, and cytokines. Given prevalent inconsistencies between in vitro, ex-vivo, and in vivo findings, we studied whether such procedures could yield misleading outcomes regarding the impact of stress hormones on NK cell cytotoxicity (NKCC), using fresh human whole blood samples. We found that in the presence of plasma 10-30-fold higher concentrations of cortisol, epinephrine, and prostaglandin-E2 (PGE2) were required to reach suppression levels evident in the context of artificial medium. Importantly, whereas the NK suppressive effects of PGE2 occurred immediately and remained stable upon prolonged exposure, the suppressive effects of cortisol slowly increased over time. Last, to simulate the exclusion of stress factors in the ex-vivo approach, we subjected whole blood to stress hormones (as occurs in vivo), and abruptly removed them. We found that the effects of epinephrine and PGE2 quickly disappeared, while the effects of cortisol persisted. Overall, these findings demonstrate the potential misleading nature of in vitro and ex-vivo procedures, and specifically suggest that (i) the common in vitro findings of profound suppression of NKCC by stress hormones are overestimation of their direct effects expected in vivo; and (ii) the common ex-vivo approach cannot reflect the direct in vivo suppressive effects of epinephrine and PGE2 on NKCC, while inflating the effects of glucocorticoids. Some of these fallacies may be circumvented by using non-delayed whole blood NKCC assays in humans.

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“…First, corticosteroid binding globulin is present only in the in vivo milieu and binds up to 90% of CORT molecules [63], reducing the effective concentrations of CORT. Second, in the in vivo milieu, but not in vitro , leukocytes continuously redistribute, enabling re-population of critical immune compartments by CORT-insensitive or unaffected cells.…”

Section: Discussionmentioning

confidence: 99%

In vivo suppression of NK cell cytotoxicity by stress and surgery: Glucocorticoids have a minor role compared to catecholamines and prostaglandins

Rosenne

Sorski

Shaashua

et al. 2014

Brain, Behavior, and Immunity

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Most in vitro and ex-vivo studies indicate a profound suppression of NK cell cytotoxicity (NKCC) by glucocorticoids; while catecholamines and prostaglandins were reported both to suppress and to enhance NKCC. However, methodological considerations hinder our ability to deduce from these findings to the impact of endogenous release of these factors on in vivo levels of NKCC and their implications to NK-dependent resistance to pathologies in living humans or animals. Here we used an in vivo approach that sensitively and specifically reflects NKCC in living F344 rats, based on lung clearance of NK-sensitive tumor cells (MADB106), and based on comparing effects between NK-intact and NK-depleted rats. To study the role of corticosterone, epinephrine, and prostaglandins, we administered these factors to rats, or antagonized their endogenous release following different stress paradigms or surgery. The results indicated that endogenous or exogenous elevated corticosterone levels can suppress in vivo NKCC levels, but only under some conditions, and mostly secondarily to the NK-suppressing impact of epinephrine. Specifically, corticosterone-induced NKCC suppression occurred (i) only under prolonged, but not short exposure to stress, and mainly in males; (ii) was smaller than the prominent impact of epinephrine; (iii) was mostly ascribed to corticosterone-induced potentiation of the effects of epinephrine or/and prostaglandins; and (iv) was completely abolished through antagonizing epinephrine or/and prostaglandins. Overall, these findings markedly limit the significance of stress/surgery-induced corticosterone release in the in vivo suppression of NKCC, and highlight the blockade of epinephrine or/and prostaglandins as effective and clinically feasible approaches to overcome such immuno-suppressive effects.

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Intact or “active” corticosteroid-binding globulin (CBG) and total CBG in plasma: Determination by parallel ELISAs using monoclonal antibodies

Cited by 32 publications

References 23 publications

Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing

Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing

The misleading nature of in vitro and ex vivo findings in studying the impact of stress hormones on NK cell cytotoxicity

In vivo suppression of NK cell cytotoxicity by stress and surgery: Glucocorticoids have a minor role compared to catecholamines and prostaglandins

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