Delivery and Transport of Glucocorticoids to Target Cells

Ballard, Pl

doi:10.1007/978-3-642-81265-1_2

Cited by 103 publications

(34 citation statements)

References 77 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%

“…In humans, administration of GC in doses of 100-500 mg results in drug levels that do not exceed 1-2 ,ig/ml for sustained time periods (12,13). Also, the peak GC level of 20 ,ug/ ml obtained in humans after infusion of 1-2 g of methylprednisolone (Upjohn Co., Kalamazoo, MI) is not comparable to a GC concentration of 16-100 jg/ml in cell culture medium sup-plemented with only 10% serum (11), since in vivo about 90% of the drug is immobilized by albumin and thus remains biologically inactive (13,14). Furthermore, in patients with Cushing's syndrome, severe opportunistic infections such as aspergillosis, nocardiosis, or listeriosis occur at cortisol levels ranging from 0.4 to 1.8 ig/ml (4)…”

Section: Introductionmentioning

confidence: 99%

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

Schaffner¹

1985

J. Clin. Invest.

197

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%

Section: Introductionmentioning

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.

197

125

View full text Add to dashboard Cite

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“…Free steroid in the tissue space is thought to dissolve in the plasma membrane and then to reappear in the cytoplasm, due to its tight binding to a specific receptor (of which, more below). Harrison, however, has presented data in one cell system at least which suggests that uptake is an active, energy-requiring process (1). In my opinion, the question of cell uptake of steroids is underinvestigated.…”

Section: April 1981mentioning

confidence: 98%

“…Most natural cortiocosteroids in fact do so in the bound form. Corticosteroid binding globulin (CBG) is a highly specific binder for this class of steroids, and the naturally occurring members of the class, and some synthetic analogs bind to CBG with high affinity (1). But corticosteroids also bind, with less specificity and affinity, to a number of plasma proteins.…”

Section: Delivery Of Corticosteroids To Target Tissuesmentioning

confidence: 99%

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Factors affecting adrenocortical hormone function.

Thompson¹

1981

Environ Health Perspect

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This paper will briefly outline those elements which must be considered in assessing the effects of any given compound which might impinge on the actions of adrencortical steroids. Considerations that ought to be taken into account include the following: the delivery to the affected cells of cortiocosteroids, the uptake of the hormone by the cells, the metabolism of the hormone by the cells, the intracellular actions of the hormone, the possible secondary interactions between cells, and multihormonal actions on the final target cell.

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HPA Axis‐Rhythms

Spiga¹,

Walker²,

Terry³

et al. 2014

Comprehensive Physiology

242

190

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The hypothalamic-pituitary-adrenal (HPA) axis regulates circulating levels of glucocorticoid hormones, and is the major neuroendocrine system in mammals that provides a rapid response and defense against stress. Under basal (i.e., unstressed) conditions, glucocorticoids are released with a pronounced circadian rhythm, characterized by peak levels of glucocorticoids during the active phase, that is daytime in humans and nighttime in nocturnal animals such as mice and rats. When studied in more detail, it becomes clear that the circadian rhythm of the HPA axis is characterized by a pulsatile release of glucocorticoids from the adrenal gland that results in rapid ultradian oscillations of hormone levels both in the blood and within target tissues, including the brain. In this review, we discuss the regulation of these circadian and ultradian HPA rhythms, how these rhythms change in health and disease, and how they affect the physiology and behavior of the organism.

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Delivery and Transport of Glucocorticoids to Target Cells

Cited by 103 publications

References 77 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.

Factors affecting adrenocortical hormone function.

HPA Axis‐Rhythms

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