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

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Abstract

Objective

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

Methods

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.

Results

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.

Conclusions

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.

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References

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  5. Van den Berghe G. Novel insights into the neuroendocrinology of critical illness. Eur J Endocrinol. 2000;143:1–13.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  15. Teng Chung T, Hinds CJ. Treatment with GH and IGF-1 in critical illness. Crit Care Clin. 2006;22:29–40.

    Article  PubMed  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  22. Abraham E. Nuclear factor-kappa B and its role in sepsis-associated organ failure. J Infect Dis. 2003;187:S364–9.

    Article  CAS  PubMed  Google Scholar 

Download references

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Correspondence to Y. Huang.

Additional information

Responsible Editor: A. Bauhofer.

C. Yi and Y. Cao contributed equally to this work.

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Yi, C., Cao, Y., Mao, S.H. et al. Recombinant human growth hormone improves survival and protects against acute lung injury in murine Staphylococcus aureus sepsis. Inflamm. Res. 58, 855–862 (2009). https://doi.org/10.1007/s00011-009-0056-0

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  • DOI: https://doi.org/10.1007/s00011-009-0056-0

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