OBJECTIVE: To investigate the effects of IL-18 therapy on severe and mild bacterial infection after burn injury. SUMMARY BACKGROUND DATA: IL-18 therapy restores IFN-gamma production in immunosuppressive mice following burn injury and up-regulate host response to LPS and experimental bacterial peritonitis. On the other hand, the overproduction of IFN-gamma could induce an exaggerated inflammation. Therefore, in this study, we focus on the beneficial and deleterious effects of IL-18-induced IFN-gamma and investigate the behavior of IL-18 in infections. METHODS: Burn injury was induced in C57BL/6 mice and then they were i.p. injected with IL-18 (0.2 microg) on alternate days. After 1 week, severe and mild infections were made in mice by an Escherichia coli challenge (5 x 10 CFU and 1 x 10 CFU i.v., respectively). RESULTS: IL-18 therapy decreased the mortality of burn-injured mice followed by a severe infection, whereas it unexpectedly increased the mortality of burned mice with a mild infection. The IL-18 therapy increased the number of liver mononuclear cells (MNCs), especially NK cells, and greatly up-regulated the impaired IFN-gamma production from the liver and spleen MNCs in mice with severe infection. Both the serum IFN-gamma concentrations recovered while the bacterial count in the liver decreased. In contrast, the serum IFN-gamma concentrations of the burned mice with mild infection did not decrease in comparison to the unburned mice, whereas IL-18 therapy greatly up-regulated the serum IFN-gamma levels in burned mice. However, IL-18 therapy significantly elevated the serum ALT and creatinine levels, thus suggesting that the mortality was induced by an exaggerated form of shock/multiorgan failure. These beneficial and deleterious effects of IL-18 therapy in mice with severe and mild infections, respectively, were all inhibited by anti-IFN-gamma Ab pretreatment. CONCLUSION: IL-18 therapy can be a potent therapeutic tool against severe bacterial infection in immunocompromised hosts, but careful attention should also be paid to its adverse effects.
OBJECTIVE: To investigate the effects of IL-18 therapy on severe and mild bacterial infection after burn injury. SUMMARY BACKGROUND DATA: IL-18 therapy restores IFN-gamma production in immunosuppressive mice following burn injury and up-regulate host response to LPS and experimental bacterial peritonitis. On the other hand, the overproduction of IFN-gamma could induce an exaggerated inflammation. Therefore, in this study, we focus on the beneficial and deleterious effects of IL-18-induced IFN-gamma and investigate the behavior of IL-18 in infections. METHODS:Burn injury was induced in C57BL/6 mice and then they were i.p. injected with IL-18 (0.2 microg) on alternate days. After 1 week, severe and mild infections were made in mice by an Escherichia coli challenge (5 x 10 CFU and 1 x 10 CFU i.v., respectively). RESULTS:IL-18 therapy decreased the mortality of burn-injured mice followed by a severe infection, whereas it unexpectedly increased the mortality of burned mice with a mild infection. The IL-18 therapy increased the number of liver mononuclear cells (MNCs), especially NK cells, and greatly up-regulated the impaired IFN-gamma production from the liver and spleen MNCs in mice with severe infection. Both the serum IFN-gamma concentrations recovered while the bacterial count in the liver decreased. In contrast, the serum IFN-gamma concentrations of the burned mice with mild infection did not decrease in comparison to the unburned mice, whereas IL-18 therapy greatly up-regulated the serum IFN-gamma levels in burned mice. However, IL-18 therapy significantly elevated the serum ALT and creatinine levels, thus suggesting that the mortality was induced by an exaggerated form of shock/multiorgan failure. These beneficial and deleterious effects of IL-18 therapy in mice with severe and mild infections, respectively, were all inhibited by anti-IFN-gamma Ab pretreatment. CONCLUSION:IL-18 therapy can be a potent therapeutic tool against severe bacterial infection in immunocompromised hosts, but careful attention should also be paid to its adverse effects.
Authors: R Nakagawa; I Nagafune; Y Tazunoki; H Ehara; H Tomura; R Iijima; K Motoki; M Kamishohara; S Seki Journal: J Immunol Date: 2001-06-01 Impact factor: 5.422
Authors: K Ogasawara; K Takeda; W Hashimoto; M Satoh; R Okuyama; N Yanai; M Obinata; K Kumagai; H Takada; H Hiraide; S Seki Journal: J Immunol Date: 1998-04-01 Impact factor: 5.422
Authors: James Lawrence Wynn; Chris S Wilson; Jacek Hawiger; Philip O Scumpia; Andrew F Marshall; Jin-Hua Liu; Irina Zharkikh; Hector R Wong; Patrick Lahni; John T Benjamin; Erin J Plosa; Jörn-Hendrik Weitkamp; Edward R Sherwood; Lyle L Moldawer; Ricardo Ungaro; Henry V Baker; M Cecilia Lopez; Steven J McElroy; Natacha Colliou; Mansour Mohamadzadeh; Daniel Jensen Moore Journal: Proc Natl Acad Sci U S A Date: 2016-04-25 Impact factor: 11.205
Authors: Marek Fol; Marcin Włodarczyk; Magdalena Kowalewicz-Kulbat; Magdalena Druszczyńska; Krzysztof T Krawczyk; Sebastian Wawrocki; Wiesława Rudnicka; Magdalena Chmiela Journal: Vaccines (Basel) Date: 2022-04-14