Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network

Abstract

Neuroendocrine hormones such as growth hormone (GH) and prolactin (PRL) have been demonstrated to accelerate the recovery of the immune response after chemotherapy and bone marrow transplantation and to enhance the restoration of immunity in individuals infected with HIV and in normal individuals with compromised immune systems associated with aging. As the mechanism of action of these hormones has been elucidated, it has become clear that they are integral members of the immunological cytokine/chemokine network and share regulatory mechanisms with a wide variety of cytokines and chemokines. The members of this cytokine network induce and can be regulated by members of the suppressor of cytokine signaling (SOCS) family of intracellular proteins. In order to take advantage of the potential beneficial effects of hormones such as GH or PRL, it is essential to take into consideration the overall cytokine network and the regulatory effects of SOCS proteins.

Figure 1. Promotion of Thymopoiesis by rhGH or rhPRL in Fetal Thymic Organ Cultures

Thymic lobes from day 14.5 gestation age C57BL/6 fetal mice were cultured for 13 days over transwell membranes containing serum-free media (Stemspan Expansion Medium, StemCell Technologies, Vancouver, CA) with the indicated concentration of rhGH (Serono Inc, Rockland, MA), rhPRL (kindly provided by Genzyme Corp., Cambridge, MA) or 10 ng/ml rhIL-7. At the end of the culture, cells were dissociated from the lobes, viable cells numbers were assessed using the Viacount method (Guava Technologies, Hayward, CA), labeled with CD45-FITC, CD4-PE and CD8-PC5 and analyzed by flow cytometry. A. Representative dotplots demonstrating normal distribution of thymocytes in lobes cultured with rhGH or rhPRL. Cells were gated on CD45+ expression. B. Significant increases in total viable cells in FTOC cultured with 10 ng/ml of rhGH (ANOVA with Dunnett’s post-hoc test p< 0.05).

Figure 1. Promotion of Thymopoiesis by rhGH or rhPRL in Fetal Thymic Organ Cultures

Thymic lobes from day 14.5 gestation age C57BL/6 fetal mice were cultured for 13 days over transwell membranes containing serum-free media (Stemspan Expansion Medium, StemCell Technologies, Vancouver, CA) with the indicated concentration of rhGH (Serono Inc, Rockland, MA), rhPRL (kindly provided by Genzyme Corp., Cambridge, MA) or 10 ng/ml rhIL-7. At the end of the culture, cells were dissociated from the lobes, viable cells numbers were assessed using the Viacount method (Guava Technologies, Hayward, CA), labeled with CD45-FITC, CD4-PE and CD8-PC5 and analyzed by flow cytometry. A. Representative dotplots demonstrating normal distribution of thymocytes in lobes cultured with rhGH or rhPRL. Cells were gated on CD45+ expression. B. Significant increases in total viable cells in FTOC cultured with 10 ng/ml of rhGH (ANOVA with Dunnett’s post-hoc test p< 0.05).