Effect of glycyrrhizin on the intratracheal infection of Klebsiella pneumoniae in NOD/scid IL-2Rγnull mice inoculated with alcoholic patient white blood cells (IRC4P.609)

Abstract

Abstract Humanized mice created with alcoholic patient white blood cells (patient chimeras) are extremely susceptible to infection with K. pneumoniae. M2Mϕ in patient WBC are responsible for impairing the host antibacterial response of the chimeras. Since glycyrrhizin is known as an inhibitor of M2Mϕ activities, in this study, the effect of glycyrrhizin on K. pneumoniae infection in these chimeras was investigated. Patient chimeras (γ-irradiated-NOD/scid IL-2Rγnull mice inoculated 5 x 106 cells/mouse of alcoholic patient WBC) were infected intratracheally with 100 CFU/mouse of K. pneumoniae, and treated with 10 mg/kg of glycyrrhizin (48 hours before and 2 h after infection, Minophargen Pharmaceutical Co., Ltd., Tokyo, Japan). In the results, severe bacterial growth was demonstrated in the liver (2.7 x 107 CFU/g organ), kidney (2.9 x 107 CFU/g organ), and spleen (1.4 x 109 CFU/g organ) of patient chimeras 24 h after the infection. Contrarily, only 0.15 - 6 x 104 CFU/g organ of the pathogen were detected in these organs of patient chimeras treated with glycyrrhizin. Similarly, bacterial growth was minimal in the organs of healthy chimeras (γ-irradiated-NOD/scid IL-2Rγnull mice inoculated with healthy donor WBC). These results suggest that K. pneumoniae infections in alcoholics may be controllable by glycyrrhizin, an inhibitor of M2Mϕ activities.