Growth hormone increases lung microvascular injury in lipopolysaccharide peritonitis rats: possible involvement of NF-kappaB activation in circulating neutrophils.
OBJECTIVE
To investigate the effects of growth hormone (GH) on NF-kappaB activity in neutrophils and neutrophils-mediated organ injury induced by lipopolysaccharide (LPS) in rats.


METHODS
Male Wistar rats challenged with or without LPS (5 mg/kg) were treated with varied doses of GH (0.5, 1.0, and 2.0 mg/kg) for 2 or 4 h. NF-kappaB activities in circulating neutrophils were measured with electrophoretic mobility shift assays (EMSA), and I-kappaB levels in circulating neutrophils were detected by Western blot. Lung neutrophils sequestration and lung microvascular permeability were measured at 4 h after LPS challenge.


RESULTS
Circulating neutrophils in LPS challenged rats had increased NF-kappaB activity and decreased I-kappaB level as compared with controls. GH dramatically increased NF-kappaB activity and I-kappaB degradation induced by LPS challenge in neutrophils. Also, subsequently, GH treatment increased lung neutrophils sequestration and lung microvascular injury induced by LPS.


CONCLUSIONS
These results suggest that treatment of GH is harmful, instead of beneficial, to LPS-induced organ injury. Increased neutrophils' NF-kappaB activity and lung neutrophils sequestration are critical in vivo mechanisms mediating GH action on LPS-induced organ injury.
Liu
Zhi-Hai
ZH
Research Institute of General Surgery, Nanjing University School of Medicine, Nanjing 210002, China.
Yu
Ying-Qun
YQ
Li
Wei-Qin
WQ
Li
Jie-Shou
JS
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D006133:Growth Substances / Q000009:adverse effects*; D020672:I-kappa B Proteins / Q000097:blood; D008070:Lipopolysaccharides; D008171:Lung Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D016328:NF-kappa B / Q000097:blood / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology*; D010538:Peritonitis / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D006133:Growth Substances; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B