A. Barbarino et al., DEXAMETHASONE INHIBITION OF INTERFERON-ALPHA-2-INDUCED STIMULATION OFCORTISOL AND GROWTH-HORMONE SECRETION IN CHRONIC MYELOPROLIFERATIVE SYNDROME, The Journal of clinical endocrinology and metabolism, 80(4), 1995, pp. 1329-1332
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.