DEXAMETHASONE INHIBITION OF INTERFERON-ALPHA-2-INDUCED STIMULATION OF CORTISOL AND GROWTH-HORMONE SECRETION IN CHRONIC MYELOPROLIFERATIVE SYNDROME

被引:17
作者
BARBARINO, A
COLASANTI, S
CORSELLO, SM
SATTA, MA
DELLACASA, S
ROTA, CA
TARTAGLIONE, R
BARINI, A
机构
[1] UNIV CATTOLICA SACRO CUORE, SCH MED, INST HAEMATOL, I-00168 ROME, ITALY
[2] UNIV CATTOLICA SACRO CUORE, SCH MED, INST BIOCHEM, I-00168 ROME, ITALY
关键词
D O I
10.1210/jc.80.4.1329
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study investigated the acute effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in adult patients affected by a chronic myeloproliferative syndrome and tried to shed some light on the mechanism by which IFN-alpha 2 stimulates cortisol and GH secretion in humans. We compared the pattern of IFN-alpha 2-induced cortisol and GH release with that elicited after the same challenge given subsequent to pretreatment with dexamethasone (Dex). We studied eight patients affected by a chronic myeloproliferative syndrome (thrombocythemia) who had been selected for treatment with IFN-alpha 2. Four sets of experiments were performed: 1) 2 mL iv saline was given at 0800 h in eight cases; 2) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h in eight cases; 3) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h after pretreatment with 1.5 mg Dex (1 mg at midnight the previous night and 0.5 mg at 0700 h on the day of the test) in six cases; and 4) 2 mL iv saline was given at 0800 h after the same Dex pretreatment in four cases. Cortisol and GH were measured in plasma samples drawn at 30-min intervals between 0800 and 1300 h. Acute iv administration of IFN-alpha 2 stimulated the release of both cortisol and GH in each patient with a significant increment vs. control values, as assessed by areas under the curve. The administration of Dex significantly decreased basal plasma cortisol secretion and abolished cortisol response to IFN-alpha 2 administration. These data suggest that the stimulatory action of IFN-alpha 2 on cortisol release is mediated via a modulation of the activity of the hypothalamic-pituitary axis rather than through a direct effect at the level of the adrenal cortex. After Dex plus saline administration, no significant effect was observed on plasma GH levels, which remained low. Dex administration significantly decreased GH response to IFN-alpha 2. These data suggest that a hypothalamic or pituitary stimulation (or both) is involved in the mechanism of IFN-alpha 2-induced GH secretion. It remains to be established whether IFN-alpha 2 directly stimulates pituitary somatotropic cells or whether the cytokine exerts a stimulatory action on GH secretion by indirectly modulating the hypothalamic or pituitary activity. In conclusion, acute iv administration of IFN-alpha 2 represents a potent stimulus for cortisol and GH secretion in adult human subjects. Dex pretreatment blunts the IFN-alpha 2-induced stimulation of cortisol and GH secretion, and this effect suggests that IFN-alpha 2 action is mediated via an activation of the hypothalamic-pituitary axis.
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页码:1329 / 1332
页数:4
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