Objective: Systemic inflammatory response syndrome(SIRS)is a pathophysiological inflammatory response mediated largely by Tumor necrosis factor-α(TNF-α)in response to infectious or non-infectious stimuli.TNF-α secretion in response to bacterial lipopolysaccharide(LPS)is regulated in part by ADAM17.Therefore,this study was undertaken to find an effective inhibitor of ADAM17 to control inflammation and related processes.Methods: A lentivirus vector expressing shRNA targeting the ADAM17 gene and containing a GFP reporter was constructed.U937 cells were transfected with the lentivirus and stimulated with LPS.ADAM17 expression was assessed by Western blotting and TNF-a secretion was assessed by ELISA.The lentivirus was also tested in vivo in a mouse model of endotoxemia,and the surface expression of immature TNF-α was assessed on peritoneal macrophages by flow cytometry following an LPS challenge.Result: The ADAM17 shRNA lentivirus reduced ADAM17 expression,and prevented maturation and secretion of TNF-a in vitro from U937 cells following an LPS challenge.In vivo,mice exposed to the ADAM17 shRNA lentivirus prior to inducing endotoxemia with LPS had fewer signs of inflammation and less tissue damage in the liver,lungs,and kidneys than control mice.The expression of(immature)TNF-a was also increased on the surface of the peritoneal macrophages from mice exposed to the ADAM17 shRNA lentivirus compared to LPS alone.Conclusion: In summary,this study successfully constructed an shRNA lentivirus vector targeting the ADAM17 gene that had clear in vitro and in vivo effects of TNF-α processing in response to an LPS challenge.These Result: s may help inform the design and improvement of drugs designed to inhibit the function of ADAM17,and suggest a novel means of controlling inflammation and its related processes.