Inflammatory status in sepsis alters efficacy of interleukin-18 binding protein therapy*
作者:
Daniel Remick,
Gerald Bolgos,
Javed Siddiqui,
期刊:
Critical Care Medicine
(OVID Available online 2003)
卷期:
Volume 31,
issue 8
页码: 2096-2101
ISSN:0090-3493
年代: 2003
出版商: OVID
关键词: sepsis;neutrophils;cytokines;lymphocytes;monocytes;interleukin-6
数据来源: OVID
摘要:
ObjectiveSepsis 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.DesignPrevious 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.SettingUniversity research laboratory.SubjectsAdult, female BALB/c mice.InterventionsWe 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 ResultsIn 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.ConclusionsIn 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.
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