Inflammation Research

, Volume 58, Issue 12, pp 855–862 | Cite as

Recombinant human growth hormone improves survival and protects against acute lung injury in murine Staphylococcus aureus sepsis

  • C. Yi
  • Y. Cao
  • S. H. Mao
  • H. Liu
  • L. L. Ji
  • S. Y. Xu
  • M. Zhang
  • Y. Huang
Original Research Paper



To investigate whether recombinant human growth hormone (rhGH) reduces mortality and protects against Staphylococcus aureus sepsis-induced acute lung injury.


The bacteria-positive rate of blood smears and bacteria colony counts in bacteria plate culture, TNFα and IL-10 plasma levels, lung injury score, expression of intercellular adhesion molecule-1 (ICAM-1) as well as activation of nuclear factor-kappa B (NF-κB) in the lungs were determined 6, 12 and 24 h after 140 KM mice were injected with physiologic saline (i.p. group C, n = 20); S. aureus E311122 (1.75 × 1012 cfu/L, 40 ml/kg, i.p. group S, n = 60); or S. aureus (as group S) with a subsequent treatment of rhGH (1.0 U kg−1 day−1), i.m. group T, n = 60). The cumulative survival rate of an additional 15 mice from each group was followed for 7 days post S. aureus injection.


rhGH treatment significantly increased IL-10 plasma levels and the 7-day cumulative survival rate, whereas the bacteria-positive rate of blood smears, bacteria colony counts in bacteria plate cultures, lung injury score, ICAM-1 and NF-κB expression in the lungs were significantly reduced. In addition, rhGH treatment significantly suppressed the S. aureus sepsis-induced elevation of TNFα plasma levels.


These results indicate an ability of rhGH to prevent S. aureus sepsis-induced acute lung injury in mice, which may be attributed to attenuation of increased plasma TNFα levels, and elevated IL-10 plasma levels as well as reduced ICAM-1 expression and inhibited NF-κB activity in the lungs.


Sepsis Growth hormone Lung injury Intercellular adhesion molecule-1 (ICAM-1) Nuclear factor-kappa B (NF-κB) 


  1. 1.
    Opal SM, Cohen J. Clinical Gram-positive sepsis: does it fundamentally differ from Gram-negative bacterial sepsis? Crit Care Med. 1999;27:1608–16.CrossRefPubMedGoogle Scholar
  2. 2.
    Hiramatsu K, Hanaki H, Ino T, Yabuta K, Oguri T, Tenover FC. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother. 1997;40:135–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Ploy MC, Grélaud C, Martin C, de Lumley L, Denis F. First clinical isolate of vancomycin-intermediate Staphylococcus aureus in a French hospital. Lancet. 1998;351:1212.CrossRefPubMedGoogle Scholar
  4. 4.
    Kolstad O, Jenssen TG, Ingebretsen OC, Vinnars E, Revhaug A. Combination of recombinant human growth hormone and glutamine-enriched total parenteral nutrition to surgical patients: effects on circulating amino acids. Clin Nutr. 2001;20:503–10.CrossRefPubMedGoogle Scholar
  5. 5.
    Van den Berghe G. Novel insights into the neuroendocrinology of critical illness. Eur J Endocrinol. 2000;143:1–13.CrossRefPubMedGoogle Scholar
  6. 6.
    Heemskerk VH, Daemen MA, Buurman WA. Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in immunity and inflammation. Cytokine Growth Factor Rev. 1999;10:5–14.CrossRefPubMedGoogle Scholar
  7. 7.
    Hattori N, Saito T, Yagyu T, Jiang BH, Kitagawa K, Inagaki C. GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J Clin Endocrinol Metab. 2001;86:4284–91.CrossRefPubMedGoogle Scholar
  8. 8.
    Mylonas PG, Matsouka PT, Papandoniou EV, Vagianos C, Kalfarentzos F, Alexandrides TK. Growth hormone and insulin-like growth factor I protect intestinal cells from radiation-induced apoptosis. Mol Cell Endocrinol. 2000;160:115–22.CrossRefPubMedGoogle Scholar
  9. 9.
    Yi C, Cao Y, Wang SR, Xu YZ, Huang H, Cui YX, et al. Beneficial effect of recombinant human growth hormone on the intestinal mucosa barrier of septic rats. Braz J Med Biol Res. 2007;40:41–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Yi C, Wang SR, Zhang SY, Yu SJ, Jiang CX, Zhi MH, et al. Effects of recombinant human growth hormone on acute lung injury in endotoxemic rats. Inflamm Res. 2006;55:491–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Huang Y, Wang SR, Yi C, Ying MY, Lin Y, Zhi MH. Effects of recombinant human growth hormone on rat septic shock with intraabdominal infection by E. coli. World J Gastroenterol. 2002;8:1134–7.PubMedGoogle Scholar
  12. 12.
    Osman MO, Kristensen JU, Jacobsen NO, Lausten SB, Deleuran B, Deleuran M, et al. A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits. Gut. 1998;43:232–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Cheng S, He S, Zhang J. The role of alveolar macrophage activation in rats with lung injury associated with acute necrotizing pancreatitis. Zhonghua Wai Ke Za Zhi. 2002;40:609–12.PubMedGoogle Scholar
  14. 14.
    Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med. 1999;341:785–92.CrossRefPubMedGoogle Scholar
  15. 15.
    Teng Chung T, Hinds CJ. Treatment with GH and IGF-1 in critical illness. Crit Care Clin. 2006;22:29–40.CrossRefPubMedGoogle Scholar
  16. 16.
    Manley MO, O’Riordan MA, Levine AD, Latifi SQ. Interleukin 10 extends the effectiveness of standard therapy during late sepsis with serum interleukin 6 levels predicting outcome. Shock. 2005;23:521–6.PubMedGoogle Scholar
  17. 17.
    Berg RD, Garlington AW. Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun. 1979;23:403–11.PubMedGoogle Scholar
  18. 18.
    Steffen EK, Berg RD, Deitch EA. Comparison of translocation rates of various indigenous bacteria from the gastrointestinal tract to the mesenteric lymph node. J Infect Dis. 1988;157:1032–8.PubMedGoogle Scholar
  19. 19.
    Vesterlund S, Karp M, Salminen S, Ouwehand AC. Staphylococcus aureus adheres to human intestinal mucus but can be displaced by certain lactic acid bacteria. Microbiology. 2006;152:1819–26.CrossRefPubMedGoogle Scholar
  20. 20.
    Wang X, Wang B, Wu J, Wang G. Beneficial effects of growth hormone on bacterial translocation during the course of acute necrotizing pancreatitis in rats. Pancreas. 2001;23:148–56.CrossRefPubMedGoogle Scholar
  21. 21.
    Li JY, Lu Y, Hu S, Sun D, Yao YM. Preventive effect of glutamine on intestinal barrier dysfunction induced by severe trauma. World J Gastroenterol. 2002;8:168–71.PubMedGoogle Scholar
  22. 22.
    Abraham E. Nuclear factor-kappa B and its role in sepsis-associated organ failure. J Infect Dis. 2003;187:S364–9.CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • C. Yi
    • 1
  • Y. Cao
    • 2
  • S. H. Mao
    • 2
  • H. Liu
    • 2
  • L. L. Ji
    • 2
  • S. Y. Xu
    • 2
  • M. Zhang
    • 2
  • Y. Huang
    • 1
  1. 1.Department of Abdominal Cancer, Huaxi HospitalSichuan UniversityChengduChina
  2. 2.Department of Pathophysiology, West China School of Preclinical and Forensic MedicineSichuan UniversityChengduChina

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