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

Abstract

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, 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. 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. 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.