Accumulating evidence suggests that hypothalamic luteinizing hormone-r
eleasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) are tw
o hypophysiotropic factors which modulate the immune response. The aim
of the present study was to determine the in vivo effects of an intra
venous bolus of LHRH and TRH on plasma interferon (IFN)-gamma producti
on in five normoprolactinemic women with irregular menstrual cycles. W
e also determined prolactin (PRL), thyrotropin (TSH), follicle stimula
ting hormone (FSH), and luteinizing hormone (LH) levels before and aft
er intravenous administration of LHRH and TRH. The results demonstrate
that intravenous bolus of LHRH/TRH increases plasma IFN-gamma levels,
with the maximum response 45 min after in vivo administration of hypo
thalamic peptides and after peak levels of adenohypophyseal hormones (
PRL: 15 min; TSH: 30 min; FSH: 30 min; LH: 30 min). In order to invest
igate a possible direct action of hypothalamic hormones on immune cell
s, we also evaluated, in the same subjects, the influence of LHRH and
TRH on IFN-gamma production by human peripheral blood mononuclear cell
s (PBMCs), collected before the intravenous administration of the pept
ides and stimulated in vitro with bacterial superantigen staphylococca
l enterotoxin A (SEA) and concanavalin A (Con A). LKRH and TRH, separa
tely and together, significantly enhanced in vitro IFN-gamma productio
n by SEA-and ConA-activated PBMCs. The present results suggest that hy
pothalamic peptides (LHRH and TRH) directly, and/or indirectly pituita
ry hormones (PRL, TSH, FSH, and LH) or IL-2, have stimulatory effect o
n IFN-gamma producing cells and are further evidence of interactions b
etween the neuroendocrine and immune systems.