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

Inflamm Res. 2009 Dec;58(12):855-62. doi: 10.1007/s00011-009-0056-0. Epub 2009 Jun 18.

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, TNFalpha 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-kappaB) 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 x 10(12) 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-kappaB expression in the lungs were significantly reduced. In addition, rhGH treatment significantly suppressed the S. aureus sepsis-induced elevation of TNFalpha 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 TNFalpha levels, and elevated IL-10 plasma levels as well as reduced ICAM-1 expression and inhibited NF-kappaB activity in the lungs.

MeSH terms

  • Acute Lung Injury / immunology
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Human Growth Hormone / genetics
  • Human Growth Hormone / metabolism
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Lung / cytology
  • Lung / metabolism
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • NF-kappa B / metabolism
  • Random Allocation
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / therapeutic use*
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Sepsis / microbiology
  • Sepsis / pathology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / pathogenicity
  • Survival Rate
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • NF-kappa B
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Human Growth Hormone
  • Intercellular Adhesion Molecule-1
  • Interleukin-10