OBJECTIVE: Sepsis remains a serious clinical problem, and multiple attempts at blocking inflammation have failed to decrease mortality rate. Interleukin-18 has been demonstrated to be an important component of the innate immune response to bacterial infections. DESIGN: Previous work demonstrated that elevated plasma concentrations of interleukin-6 obtained in the first 6 hrs of sepsis predict a worse outcome. Mice were subjected to cecal ligation and puncture and, on the basis of the plasma concentration of interleukin-6, were randomized to receive either interleukin-18 binding protein or vehicle approximately 8 hrs after the onset of sepsis. SETTING: University research laboratory. SUBJECTS: Adult, female BALB/c mice. INTERVENTIONS: We sought to determine the role of interleukin-18 in sepsis by blocking its biological activity with the interleukin-18 binding protein in the murine model of sepsis induced by cecal ligation and puncture. MEASUREMENTS AND MAIN RESULTS: In this study, elevated plasma concentrations of interleukin-6 were associated with a worse outcome. Treatment with interleukin-18 binding protein decreased inflammation as determined by lower concentrations of plasma interleukin-6 obtained 48 hrs after the onset of sepsis. In mice with increased risk of dying, interleukin-18 binding protein slightly decreased mortality rate. However, in those mice with a predicted low mortality rate, interleukin-18 binding protein significantly increased mortality rate. CONCLUSIONS: In this study, mice at low risk of death due to sepsis had decreased survival when treated with interleukin-18 binding protein. These results have potential implications for the use of interleukin-18 binding protein for treatment of chronic inflammatory conditions since it may place the host at increased risk of infectious complications.
OBJECTIVE:Sepsis remains a serious clinical problem, and multiple attempts at blocking inflammation have failed to decrease mortality rate. Interleukin-18 has been demonstrated to be an important component of the innate immune response to bacterial infections. DESIGN: Previous work demonstrated that elevated plasma concentrations of interleukin-6 obtained in the first 6 hrs of sepsis predict a worse outcome. Mice were subjected to cecal ligation and puncture and, on the basis of the plasma concentration of interleukin-6, were randomized to receive either interleukin-18 binding protein or vehicle approximately 8 hrs after the onset of sepsis. SETTING: University research laboratory. SUBJECTS: Adult, female BALB/c mice. INTERVENTIONS: We sought to determine the role of interleukin-18 in sepsis by blocking its biological activity with the interleukin-18 binding protein in the murine model of sepsis induced by cecal ligation and puncture. MEASUREMENTS AND MAIN RESULTS: In this study, elevated plasma concentrations of interleukin-6 were associated with a worse outcome. Treatment with interleukin-18 binding protein decreased inflammation as determined by lower concentrations of plasma interleukin-6 obtained 48 hrs after the onset of sepsis. In mice with increased risk of dying, interleukin-18 binding protein slightly decreased mortality rate. However, in those mice with a predicted low mortality rate, interleukin-18 binding protein significantly increased mortality rate. CONCLUSIONS: In this study, mice at low risk of death due to sepsis had decreased survival when treated with interleukin-18 binding protein. These results have potential implications for the use of interleukin-18 binding protein for treatment of chronic inflammatory conditions since it may place the host at increased risk of infectious complications.
Authors: Kendra N Iskander; Marcin F Osuchowski; Deborah J Stearns-Kurosawa; Shinichiro Kurosawa; David Stepien; Catherine Valentine; Daniel G Remick Journal: Physiol Rev Date: 2013-07 Impact factor: 37.312
Authors: W Joost Wiersinga; Catharina W Wieland; Gerritje J W van der Windt; Anita de Boer; Sandrine Florquin; Arjen Dondorp; Nicholas P Day; Sharon J Peacock; Tom van der Poll Journal: Infect Immun Date: 2007-05-21 Impact factor: 3.441