Relationship between Growth Hormone and Cytokines in Short Children Undergoing Growth Hormone Stimulation Testing


Background: The relationship between growth hormone (GH) and cytokines remains unclear. Several studies have suggested that GH increases tumor necrosis factor (TNF)-α production in both children and adults. However, a number of studies have demonstrated a negative correlation between GH and TNF α. The aim of this study is to explore the relationship between endogenous GH secretion and certain pro and anti-inflammatory cytokines in short children undergoing GH stimulation testing for evaluation for GH deficiency. Methods: Plasma growth hormone, TNF α, CRP, IL-6, IL1-β, IL-4 and IL-10 levels are obtained at baseline and every 30 minutes for 150 minutes following two provocative agents (clonidine, and either arginine or glucagon). Results: Among the 23 children, 7 are found to be GH deficient. No significant differences in baseline TNF α levels are found between GH deficient and GH sufficient children. No correlation is identified between TNF α levels and GH levels during stimulation testing. Furthermore, no relationship is found between GH and pro-inflammatory cytokines or GH and anti-inflammatory cytokines. Conclusion: Our results do not demonstrate an acute relationship between endogenous GH secretion and the cytokines examined.

Share and Cite:

Tafuri, K. , Dixon, D. , Markarian, K. , Lane, A. and A. Wilson, T. (2015) Relationship between Growth Hormone and Cytokines in Short Children Undergoing Growth Hormone Stimulation Testing. International Journal of Clinical Medicine, 6, 912-918. doi: 10.4236/ijcm.2015.612119.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Walton, P.E. and Cronin, M.J. (1989) Tumor Necrosis Factor-Alpha Inhibits Growth Hormone Secretion from Cultured Anterior Pituitary Cells. Endocrinology, 125, 925-929.
[2] Scarborough, D. (1990) Cytokine Modulation of Pituitary Hormone Secretion. Annals of the New York Academy of Sciences, 594, 169-187.
[3] Edwards, C.K., et al. (1991) Hypophysectomy Inhibits the Synthesis of Tumor Necrosis Factor Alpha by Rat Macrophages: Partial Restoration by Exogenous Growth Hormone or Interferon Gamma. Endocrinology, 128, 989-986.
[4] Kooijman, R., et al. (1992) Expression of Type I Insulin-Like Growth Factor Receptors on Human Peripheral Blood Mononuclear Cells. Endocrinology, 131, 2244-2250.
[5] Bozzola, M., et al. (2003) Stimulating Effect of Growth Hormone on Cytokine Release in Children. European Journal of Endocrinology, 149, 397-401.
[6] Pagani, S., et al. (2005) Serum Cytokine Levels in GH-Deficient Children during Substitutive GH Therapy. European Journal of Endocrinology, 152, 207-210.
[7] Ramos, S.B., Brenu E.W., Christy, R., et al. (2011) Assessment of Immune Function after Short Term Administration of Recombinant Growth Hormone in Healthy Young Males. European Journal of Applied Physiology, 111, 1307-1312.
[8] Michalacos, S., et al. (2002) Tumor Necrosis Factor-Alpha Levels in Short Children. Journal of Pediatric Endocrinology and Metabolism, 15, 193-196.
[9] Andiran, N. and Yordam, N. (2007) TNF-Alpha Levels in Children with Growth Hormone Deficiency and the Effect of Long-Term Growth Hormone Replacement Therapy. Growth Hormone & IGF Research, 17, 149-153.
[10] Zarkesh-Esfahani, S.H., et al. (2000) High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-Alpha, Interleukin-6, and Interferon-Gamma) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress. Journal of Clinical Endocrinology & Metabolism, 85, 3383-3390.
[11] Bozzola, M., De Amici, M., Zecca, M., Schimpff, R. and Rapaport, R. (1998) Modulating Effect of Human Growth Hormone on Tumour Necrosis Factor-Alpha and Interleukin-1β. European Journal of Endocrinology, 138, 640-643.
[12] Chrysopoulo, M.T., Jeschke, M.G., Ramirez, R.J., et al. (1999) Growth Hormone Attenuates Tumor Necrosis Factor Alpha in Burned Children. Archives of Surgery, 134, 283-286.
[13] Hardin, D.S., Ellis, K.J., Dyson, M., et al. (2001) Growth Hormone Decreases Protein Catabolism in Children with Cystic Fibrosis. The Journal of Clinical Endocrinology & Metabolism, 86, 4424-4428.
[14] Ross, R. (1993) The Pathogenesis of Atherosclerosis: A Perspective for the 1990s. Nature, 362, 801-809.
[15] Serri, O., St-Jacques, P., Sartippour, M., et al. (1999) Alterations of Monocyte Function in Patients with Growth Hormone (GH) Deficiency: Effect of Substitutive GH Therapy. The Journal of Clinical Endocrinology & Metabolism, 84, 58-63.
[16] Lanes, R., Paoli, M., Carrillo, E., et al. (2004) Peripheral Inflammatory and Fibrinolytic Markers in Adolescents with Growth Hormone Deficiency: Relation to Postprandial Dyslipidemia. Journal of Pediatrics, 145, 657-661.
[17] Nader, N.D., Ignatowski, T.A., Kurek, C.J., et al. (2001) Clonidine Suppresses Plasma and Cerebrospinal Fluid Concentrations of TNF-Alpha during the Perioperative Period. Anesthesia & Analgesia, 93, 363-369.
[18] Xu, B., Thornton, C., Makris, A., Ogle, R. and Hennessy, A. (2007) Anti-Hypertensive Drugs Alter Cytokine Production from Preeclamptic Placentas and Peripheral Blood Mononuclear Cells. Hypertension in Pregnancy, 26, 343-356.
[19] Xu, B., Makris, A., Thornton, C., et al. (2006) Antihypertensive Drugs Clonidine, Diazoxide, Hydralazine and Furosemide Regulate the Production of Cytokines by Placentas and Peripheral Blood Mononuclear Cells in Normal Pregnancy. Journal of Hypertension, 24, 915-922.
[20] Spengler, R.N., Allen, R.M., Remick, D.G., Strieter, R.M. and Kunkel, S.L. (1990) Stimulation of Alpha-Adrenergic Receptor Augments the Production of Macrophage-Derived Tumor Necrosis Factor. Journal of Hypertension, 145, 1430-1434.
[21] Oliver, J.C., Bland, L.A., Oettinger, C.W., et al. (1993) Cytokine Kinetics in an in Vitro Whole Blood Model Following an Endotoxin Challenge. Lymphokine & Cytokine Research, 12, 115-120.
[22] Kappel, M., Hansen, M.B., Diamant, M., et al. (1993) Effects of an Acute Bolus Growth Hormone Infusion on the Human Immune System. Hormone and Metabolic Research, 25, 579-585.
[23] Tripathi, A. and Sodhi, A. (2009) Growth Hormone-Induced Production of Cytokines in Murine Peritoneal Macrophages in Vitro: Role of JAK/STAT, PI3K, PKC and MAP Kinases. Immunobiology, 214, 430-440.
[24] Rosenblum, M.G. and Donato, N.J. (1989) Tumor Necrosis Factor Alpha: A Multifaceted Peptide Hormone. Critical Reviews in Immunology, 9, 21-44.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.