Growth hormone increases lung NF-kappaB activation and lung microvascular injury induced by lipopolysaccharide in rats.
The purpose of this study was to examine the effects of growth hormone (GH) on nuclear factor kappa B (NF-kappaB) activation and organ injury induced by lipopolysaccharide (LPS) in rats. Male Wistar rats were divided into 6 groups treated with saline, LPS (5 mg/kg), LPS plus GH (0.5, 1.0, 2.0 mg/kg), or GH (2.0 mg/kg) alone for 2 or 4 hr. NF-kappaB activity and I-kappaB level in lung, lung accumulation of neutrophils, and lung microvascular injury were measured. LPS-challenged rats had increased NF-kappaB activity and decreased I-kappaB level in lung, compared to controls. GH dramatically enhanced NF-kappaB activation and I-kappaB degradation induced by LPS challenge. LPS plus GH treatment increased lung accumulation of neutrophils, compared with LPS treatment. Also, subsequently, GH treatment increased lung microvascular injury induced by LPS. These findings suggest that treatment with GH is harmful, instead of beneficial, to LPS-induced organ injury. Increased NF-kappaB activation may be a critical in vivo mechanism that mediates GH action on LPS-induced organ injury. Thus, it is appropriate to rethink GH administration in critical illnesses; further studies are required to evaluate the safety and clinical benefits of GH administration in such conditions.
Liu
Zhihai
Z
Department of Surgery, Nanjing University College of Medicine, China.
Yu
Yingqun
Y
Jiang
Yun
Y
Li
Jieshou
J
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D010538:Peritonitis / Q000139:chemically induced / Q000150:complications / Q000276:immunology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000139:chemically induced / Q000150:complications / Q000276:immunology
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D013006:Growth Hormone