[Effect of growth hormone on acute lung injury].

OBJECTIVE: To study the effect of growth hormone (GH) on acute lung injury (ALI) induced by endotoxemia, and its potential therapeutic mechanism.

METHODS: One hundred and twelve male Sprague-Dawley rats were randomly divided into ALI group and GH group. The rats in two groups were further divided into seven subgroups determined by the length of interval after lipopolysaccharide (LPS) challenge: 0 (before injection of LPS, served as control group), 0.5, 1, 2, 4, 6 and 24 hours subgroups respectively. Pulmonary alveolar septum area density (PASAD) and the number of neutrophil in lungs of rats were analyzed morphometrically. The levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were determined by radioimmunoassay. The expression and activation of nuclear factor-kappaB (NF-kappaB) were analyzed, NF-kappaB positive cells in lungs were counted after immunofluorescence staining, and the levels of NF-kappaB inhibition (I-kappaB alpha) in lung homogenates of rats were assayed by Western blot.

RESULTS: Half an hour after intravenous injection of LPS, both the PASAD and the number of neutrophil in lungs of ALI rats began to increase, and peaked at 6 hours post-injury, then began to recover and reached the normal levels at 24 hours. The content of TNF in lung homogenates showed immediate elevation after LPS injection, becoming higher than that of the control after 0.5 hour, reaching the peak value at 1 hour, maintaining high levels until 6 hours, then gradually recovered. The content of TNF in lung homogenates of the GH group increased significantly more than that in the LPS group. The contents of IL-6 in rats' lung homogenates began to increase significantly 1 hour post-injury, peaked at 4 hours, then gradually returned to normal level 6 hours post-injury. The content of IL-6 in the lung homogenates of GH group was higher than that in the LPS group at different time intervals post-injury, showing significant difference at 0.5, 6 and 24 hours (P<0.05 or P<0.01). The number of NF-kappaB positive cells increased dramatically at 0.5 hour post-injury. The intensity of fluorescence was enhanced. Both of them peaked at 4 hours post-injury. The number of NF-kappaB positive cells and the enhanced intensity of fluorescence began to decrease at 6 hours post-injury. But the number of NF-kappaB cells at 24 hours post-injury was still larger than that in the control group. The number of NF-kappaB cells in lungs of GH group was significantly larger than that in the LPS group at different time intervals post-injury (P<0.05 or P<0.01). I-kappaB alpha contents in lung homogenates of ALI rats decreased dramatically 0.5 hour post-injury, nadir at 4 hours, and then began to recover. Correlation analysis indicated that PASAD, the levels of TNF and IL-6 and the extent of neutrophil infiltration in lung were positively correlated to the extent of the expression and the activation of NF-kappaB.

CONCLUSION: The application of GH during early stage of endotoxin challenge can deteriorate the lung injury induced by LPS through enhancing the expression and activation of NF-kappaB, thus enhances the inflammatory response in lungs.