AIM： To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. METHODS： Peripheral blood mononuclear cells of 20 out-pa...AIM： To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. METHODS： Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis,Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like receptor 2 and 4 expression was determined by flow cytometry, and tumor necrosis factor （TNF） α, interleukin （1L）-1β, IL-6, IL-12 and IL-10 secretion in su- pernatants was determined by ELISA. RESULTS： Higher CD14, Toll-like receptor 2 and 4 expression was observed in peripheral blood mononudear cells from cirrhotic patients, （P 〈 0.01, P 〈 0.006, P 〈 0.111） respectively. Lipopolysaccharide and lipoteichoic acid induced a further increase in CD14 expression （P 〈 0.111 lipopolysaccharide, P 〈 0.013 lipoteichoic acid）, and a decrease in Toll-like receptor 2 （P 〈 0.008 lipopolysaccharide, P 〈 0.008 lipoteichoic acid） and Toll-like receptor 4 （P 〈 0.008 lipopolysaccharide, P 〈 0.028 li- poteichoic acid） expression. With the exception of TNFα, absolute cytokine secretion of peripheral blood mononuclear cells was lower in cirrhotic patients under nonexposure conditions （P 〈 0.070 IL-6, P 〈 0.009 IL-1]5, P 〈 0.022 IL-12）. Once exposed to lipopolysaccharide or lipoteichoic acid, absolute cytokine secretion of peripheral blood mononuclear cells was similar in cirrhotic and non-cirrhotic patients, determining a more vigorous response in the former （P 〈 0.005 TNFα, IL-1β, IL-6, IL-2 and IL-10 lipopolysaccharide; P 〈 0.037 TNFα; P 〈 0.006 IL-113; P 〈 0.005 IL-6; P 〈 0.007 IL-12; P 〈 0.014 IL-10 lipoteichoic acid）. Response of peripheral blood mononuclear cells was more intense after lipopolysaccharide than after lipoteichoic acid exposure. CONCLUSION： Peripheral blood mononuclear cells of cirrhotic patients are able to respond to a sudden bacterial ligand exposure, particularly lipopolysaccharide, suggesting that immune regulation mechanisms are still present.展开更多
基金Supported by a Grant from the Consejo Nacional de Ciencia y Tecnología CONACyT-DAIC-48401-M, México
文摘AIM： To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. METHODS： Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis,Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like receptor 2 and 4 expression was determined by flow cytometry, and tumor necrosis factor （TNF） α, interleukin （1L）-1β, IL-6, IL-12 and IL-10 secretion in su- pernatants was determined by ELISA. RESULTS： Higher CD14, Toll-like receptor 2 and 4 expression was observed in peripheral blood mononudear cells from cirrhotic patients, （P 〈 0.01, P 〈 0.006, P 〈 0.111） respectively. Lipopolysaccharide and lipoteichoic acid induced a further increase in CD14 expression （P 〈 0.111 lipopolysaccharide, P 〈 0.013 lipoteichoic acid）, and a decrease in Toll-like receptor 2 （P 〈 0.008 lipopolysaccharide, P 〈 0.008 lipoteichoic acid） and Toll-like receptor 4 （P 〈 0.008 lipopolysaccharide, P 〈 0.028 li- poteichoic acid） expression. With the exception of TNFα, absolute cytokine secretion of peripheral blood mononuclear cells was lower in cirrhotic patients under nonexposure conditions （P 〈 0.070 IL-6, P 〈 0.009 IL-1]5, P 〈 0.022 IL-12）. Once exposed to lipopolysaccharide or lipoteichoic acid, absolute cytokine secretion of peripheral blood mononuclear cells was similar in cirrhotic and non-cirrhotic patients, determining a more vigorous response in the former （P 〈 0.005 TNFα, IL-1β, IL-6, IL-2 and IL-10 lipopolysaccharide; P 〈 0.037 TNFα; P 〈 0.006 IL-113; P 〈 0.005 IL-6; P 〈 0.007 IL-12; P 〈 0.014 IL-10 lipoteichoic acid）. Response of peripheral blood mononuclear cells was more intense after lipopolysaccharide than after lipoteichoic acid exposure. CONCLUSION： Peripheral blood mononuclear cells of cirrhotic patients are able to respond to a sudden bacterial ligand exposure, particularly lipopolysaccharide, suggesting that immune regulation mechanisms are still present.
