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

This study investigated the acute effects of interferon-alpha 2 (IFN-a lpha 2) on hormonal secretion in adult patients affected by a chronic myeloproliferative syndrome and tried to shed some light on the mechan ism by which IFN-alpha 2 stimulates cortisol and GH secretion in human s. We compared the pattern of IFN-alpha 2-induced cortisol and GH rele ase with that elicited after the same challenge given subsequent to pr etreatment with dexamethasone (Dex). We studied eight patients affecte d by a chronic myeloproliferative syndrome (thrombocythemia) who had b een 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 wit h 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 in crement vs. control values, as assessed by areas under the curve. The administration of Dex significantly decreased basal plasma cortisol se cretion and abolished cortisol response to IFN-alpha 2 administration. These data suggest that the stimulatory action of IFN-alpha 2 on cort isol release is mediated via a modulation of the activity of the hypot halamic-pituitary axis rather than through a direct effect at the leve l of the adrenal cortex. After Dex plus saline administration, no sign ificant effect was observed on plasma GH levels, which remained low. D ex administration significantly decreased GH response to IFN-alpha 2. These data suggest that a hypothalamic or pituitary stimulation (or bo th) is involved in the mechanism of IFN-alpha 2-induced GH secretion. It remains to be established whether IFN-alpha 2 directly stimulates p ituitary somatotropic cells or whether the cytokine exerts a stimulato ry action on GH secretion by indirectly modulating the hypothalamic or pituitary activity. In conclusion, acute iv administration of IFN-alp ha 2 represents a potent stimulus for cortisol and GH secretion in adu lt human subjects. Dex pretreatment blunts the IFN-alpha 2-induced sti mulation of cortisol and GH secretion, and this effect suggests that I FN-alpha 2 action is mediated via an activation of the hypothalamic-pi tuitary axis.