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Growth Hormone Increases Lung NF-B Activation and Lung Microvascular Injury Induced by Lipopolysaccharide in Rats

Address correspondence to Jieshou Li, M.D., Research Institute of General Surgery, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, P. R. China; tel 86 25 482 4804; fax 86 25 480 3956; e-mail Lijiesou{at}publicl.ptt.js.cn.

The purpose of this study was to examine the effects of growth hormone (GH) on nuclear factor kappa B (NF-B) 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-B activity and I-B level in lung, lung accumulation of neutrophils, and lung microvascular injury were measured. LPS-challenged rats had increased NF-B activity and decreased I-B level in lung, compared to controls. GH dramatically enhanced NF-B activation and I-B 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-B 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.

Keywords: growth hormone, NF-B, neutrophil, lipopolysaccharide, lung injury

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