Immune function in hypopituitarism: time to reconsider?

Abstract

Hypopituitarism is not currently considered as a potential cause of immune disruption in humans. Accumulating data from in vitro and animal models support a role for the pituitary gland in immune regulation. Furthermore, the increased mortality risk noted in patients with adult hypopituitarism remains poorly explained and immune dysfunction could conceivably contribute to this observation. In a recent issue of Clinical & Experimental Immunology, we presented new data relating to immune status in adults with treated, severe hypopituitarism. We observed humoral immune deficiency in a significant proportion, despite stable pituitary replacement, including growth hormone (GH). This was especially evident in those with low pretreatment IGF-I levels and appeared independent of anticonvulsant use or corticosteroid replacement. These observations require substantiation with future studies. In this short review, we summarize existing data relating to the effects of pituitary hormones on immune function and discuss potential clinical implications surrounding the hypothesis of immune dysregulation in severe hypopituitarism.

Enhanced immunological response by dendritic cells in male hypogonadism

“…These findings support the hypothetical contribution of the neuroendocrine axis to innate immunity, as recently suggested in human severe hypopituitarism [31]. Other pituitary hormones such as GH, corticotropin and prolactin, but not gonadotropins, have also been identified as potential candidate hormone mediators of disruption of immune homoeostasis in these patients [31]. Other pituitary hormones such as GH, corticotropin and prolactin, but not gonadotropins, have also been identified as potential candidate hormone mediators of disruption of immune homoeostasis in these patients [31].…”

“…These findings support the hypothetical contribution of the neuroendocrine axis to innate immunity, as recently suggested in human severe hypopituitarism [31]. These findings support the hypothetical contribution of the neuroendocrine axis to innate immunity, as recently suggested in human severe hypopituitarism [31].…”

Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways

“…In these studies, GH treatment has been found to diminish Fas-mediated cell death via increasing the expression of Bcl-2 and inhibiting the activation of caspase 3 [38] and to protect lymphocytes from irradiation- [39] and methyl methanesulfonate- [40] induced cell death. Several excellent reviews summarize the various effects of GH on immune cells and function [23-27; 41-44]. …”

GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

“…The vast majority of clinical and experimental studies have focused on stages with increased inflammation where it seems that chronic inflammation suppresses the GH/IGF1 axis (2,5,6,7,8,9). In addition, more recent observations have demonstrated that the relationship may be bidirectional, with GH/IGF1 activity influencing inflammatory processes (3,10,11). However, the association seems complicated as data obtained from in vivo and in vitro studies have been supporting pro-inflammatory (3,12,13) as well as anti-inflammatory effects of GH and IGF1 (3,13,14,15).…”