SUN-253 Effects of Growth Hormone Stimulation on the Immunologic Cellular Landscape in Pediatric Patients

Abstract

Background: Multiple complex interactions exist between growth hormone (GH)-Insulin like growth factor-1 axis and the immune system. We and others have demonstrated GH receptors on the cell surface of peripheral blood mononuclear cells, human IM-9 cultured lymphocytes, thymus, spleen and lymph nodes. Administration of GH to GH deficient (GHD) children has shown a transient decrease in percent B cells and T cell percentages, interleukin-2 receptor levels and lymphocyte mitogenic stimulation response. Data about acute effects of GH on the immune system are lacking. Aim: The aim of this study was to evaluate the acute effect of endogenous GH on the cellular landscape of the immune system. Methods: A prospective study was conducted in pediatric patients being evaluated for short stature who underwent a standard 3-hour growth hormone stimulation test using arginine and glucagon. Exclusion criteria included genetic syndromes, renal failure, recent immunosuppressant or steroid use and small for gestational age. Blood samples for immunologic markers, that included complete blood count (CBC) and time of flight mass flow cytometry (CyTOF), were collected at the beginning (T0) and end (T3) of the test. Differences in patients by time point (T0 and T3) and by GH response to stimulation (growth hormone sufficient {GHS} versus GHD) were calculated using a two-way ANOVA test with repeated measures over time, considering the interaction between time point and GH status. Results: Fifty-four patients (39 boys, 15 girls) aged 5-18 years, were enrolled in the study. Twenty-two participants had peak GH level <10 ng/ml (GHD). Both GHD and GHS groups were not statistically different in age, gender, pubertal status, height standard deviations (SDs), weight SDs, BMI and IGF-1 SD values, but did differ in growth velocity. Absolute lymphocyte count, lymphocyte percentage, absolute eosinophil count, absolute monocyte count and platelet count demonstrated significant (p<0.05) decrease from T0 to T3. Consistent with CBC analysis, CyTOF analysis showed a decrease (p<0.05) from T0 to T3 in percentages of B cells, monocytes, plasmacytoid dendritic cells, T helper cells and a subset of cytotoxic T cells with low CD57 expression. These results are consistent with previous reports of chronic GH administration. Total white blood cell (WBC) count, absolute neutrophil count and neutrophil percentage demonstrated increase (P<0.05) from T0 to T3, as did granulocyte percentage by CyTOF. Overall, no significant differences were found between CBC or CyTOF measurements and GH status at either time point (T0 and T3). Conclusions: The study provides the first high-resolution map of acute changes in the immune system with GH stimulation. CBC and CyTOF analyses showed significant changes, consistent with previous studies during chronic GH administration. No significant differences were observed between the GHD and GHS groups.