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
Opal SM, Cohen J. Clinical Gram-positive sepsis: does it fundamentally differ from Gram-negative bacterial sepsis? Crit Care Med. 1999;27:1608–16.
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.
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.
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.
Van den Berghe G. Novel insights into the neuroendocrinology of critical illness. Eur J Endocrinol. 2000;143:1–13.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Teng Chung T, Hinds CJ. Treatment with GH and IGF-1 in critical illness. Crit Care Clin. 2006;22:29–40.
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.
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.
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.
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.
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.
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.
Abraham E. Nuclear factor-kappa B and its role in sepsis-associated organ failure. J Infect Dis. 2003;187:S364–9.
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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