Growth Hormone (GH) Deficient Mice With GHRH Gene Ablation Are Severely Deficient in Vaccine and Immune Responses Against Streptococcus pneumoniae

Abstract

The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene (Ghrh−/−) have normal thymus and T-cell development, but present a marked spleen atrophy and B-cell lymphopenia. Therefore, in this paper we have investigated vaccinal and anti-infectious responses of Ghrh−/− mice against S. pneumoniae, a pathogen carrying T-independent antigens. Ghrh−/− mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, PPV23) or protein-PPS conjugate (PCV13). GH supplementation of Ghrh−/− mice restored IgM response to PPV23 vaccine but not to PCV13 suggesting that GH could exert a specific impact on the spleen marginal zone that is strongly implicated in T-independent response against pneumococcal polysaccharides. As expected, after administration of low dose of S. pneumoniae, wild type (WT) completely cleared bacteria after 24 h. In marked contrast, Ghrh−/− mice exhibited a dramatic susceptibility to S. pneumoniae infection with a time-dependent increase in lung bacterial load and a lethal bacteraemia already after 24 h. Lungs of infected Ghrh−/− mice were massively infiltrated by inflammatory macrophages and neutrophils, while lung B cells were markedly decreased. The inflammatory transcripts signature was significantly elevated in Ghrh−/− mice. In this animal model, the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in vaccine and immunological defense against S. pneumoniae.

Novel causes and consequences of overtraining syndrome: the EROS-DISRUPTORS study

“…The basic immunology panel was also independently affected by the presence of OTS, which supports the theory of involvement of the immune system in the pathophysiology of OTS. Although altered immunology panels (i.e., altered when compared with healthy athletes, but similar to those of non-athletes) may be linked to blunted hormonal responses to stress [23, 24], the immunology panel and the hormonal responses to stimulation did not exhibit linear correlations or predictions, at least for the immunologic markers analyzed in the present study: neutrophils, lymphocytes, and the neutrophil-to-lymphocyte ratio. Other mechanisms, such as an environment with chronic stressors leading to OTS may directly predict leukocyte composition [25].…”

Growth hormone-mediated reprogramming of macrophage transcriptome and effector functions

“…On the contrary, this phenotype might reflect impairment of the innate immune system, which could increase susceptibility to infectious disease. Mice with disruption of the GH releasing hormone gene have lower proportion of lung macrophages than WT mice, however in the spleen more macrophages were observed 11 . These mice also exhibited increased susceptibility to S. pneumoniae infection with a time-dependent increase in lung bacterial load 11 .…”

“…Mice with disruption of the GH releasing hormone gene have lower proportion of lung macrophages than WT mice, however in the spleen more macrophages were observed 11 . These mice also exhibited increased susceptibility to S. pneumoniae infection with a time-dependent increase in lung bacterial load 11 . GH-deficient Snell dwarf mice, despite having absent GH pituitary secretion, do have expression of GH in bone marrow cells 12 .…”

Case Report: SARS-CoV-2 Infection in a Child With Suprasellar Tumor and Hypothalamic-Pituitary Failure

“…Due to the recent diagnosis, despite her GH deficiency, our patient at the time of the SARS-CoV-2 infection had not yet started treatment. Although infections can cause GH deficiency ( 15 ), there is no data in the literature on the increased risk of infections in patients with GH deficiency. Critical illness induced a rise in GH and IGFBP1 and a fall in IGF-I and IGFBP3, as previously described.…”