Severe deficiency of the somatotrope GHRH/GH/IGF-1 axis induces a dramatic susceptibility to Streptococcus pneumoniae infection.

Deletion of the growth hormone-releasing hormone gene (Ghrh) results in a severe deficiency of the somatotrope GHRH-GH-IGF-1 axis causing dwarf phenotype that can be reversed by GH or GHRH supplementation (Alba & Salvatori, Endocrinology 2004;145:4134). In basal conditions, the immunological phenotype of Ghrh-/- mice is not markedly disturbed except for a decrease in B cells and an increase in generation of thymic (t) Treg cells (submitted for publication). These data prompted us to investigate immune responses of Ghrh-/- mice using vaccination and infection by S. pneumoniae as models since the response to both stimuli rely on the innate immune system and B cells.
Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH differently impacts on B-1, marginal zone B-2 or innate B-1 B cells. Furthermore, after intranasal instillation of a non-lethal dose of serotype 1 S. pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility reflected by bacteremia 24h after infection and a survival limit of 72 h, compared to WT C57BL/6 mice that need only 24h to clear infection. The possible impact of GH deficiency on components of the innate immune system that play an important role in defense of the respiratory tract against pneumococcal infection is under current investigation.
(*Equal first and last authors. KF is supported by a research grant from the Lebanese Government; GB is Research Assistant, CD is Research Associate, and VG is Research Director at the NFSR of Belgium).