当前位置： SCI文献检索 > BRITISH JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Suppression of human monocyte tumour necrosis factor-alpha release by glucocorticoid therapy: relationship to systemic monocytopaenia and cortisol suppression.

Suppression of human monocyte tumour necrosis factor-alpha release by glucocorticoid therapy: relationship to systemic monocytopaenia and cortisol suppression.

Abstract：

AIMS:Glucocorticoids suppress the release of tumour necrosis factor-alpha (TNF-alpha) by macrophages in vitro and cause monocytopaenia in vivo. These actions may contribute to anti-inflammatory and immunosuppressant effects. We therefore examined relationships between prednisolone concentration, suppression of monocyte TNF-alpha release, monocytopaenia and suppression of total cortisol concentration in healthy volunteers treated with a single dose (1.5 mg kg-1) of the glucocorticoid, prednisolone. METHODS:Monocyte numbers, total cortisol concentration and prednisolone concentration were measured in blood samples collected over 48 h after the dose. Plasma from these samples was also tested for its capacity to suppress lipopolysaccharide-induced TNF-alpha release from monocytes in autologous whole blood cultures. RESULTS:At 4 h after the dose, monocyte numbers in peripheral blood had fallen to a mean of 18% of the pre-dose level whilst plasma total cortisol had fallen to 9% of the pre-dose concentration. Monocyte numbers recovered in concordance with elimination of prednisolone and there was a significant relative monocytosis at 24 h. The recovery of plasma cortisol was delayed in comparison, with cortisol remaining significantly suppressed at 24 h. Plasma samples taken at 2 h after the dose (corresponding to peak plasma prednisolone concentration) suppressed the lipopolysaccharide-stimulated production of TNF-alpha by autologous blood monocytes to 27% of pre-dose control. Plasma collected at intervals over the 48 h from dosing also suppressed monocyte TNF-alpha release in relation to the prednisolone concentration therein. Suppression was largely reversed by the glucocorticoid antagonist, mifepristone. A similar relationship between prednisolone concentration and TNF-alpha suppression was observed when prednisolone was added to blood samples collected from the volunteers when they were drug-free. CONCLUSIONS:Blood concentration of prednisolone achieved after a dose of 1.5 mg kg-1 are sufficient to suppress monocyte TNF-alpha release and cause a biphasic change in peripheral blood monocyte numbers. Suppression of TNF-alpha is principally a direct glucocorticoid effect, rather than a consequence of other prednisolone-induced changes to blood composition.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Steer JH,Vuong Q,Joyce DA

doi

10.1046/j.1365-2125.1997.00586.x

subject

Has Abstract

pub_date

1997-04-01 00:00:00

pages

383-9

issue

eissn

0306-5251

issn

1365-2125

journal_volume

pub_type

临床试验,杂志文章

在线工具

Suppression of human monocyte tumour necrosis factor-alpha release by glucocorticoid therapy: relationship to systemic monocytopaenia and cortisol suppression.