Inhibiting early activation of tissue nuclear factor-κB and nuclear factor interleukin 6 with (1→3)-β-D -glucan increases long-term survival in polymicrobial sepsis

• Published in: Surgery 1999-07, Vol.126 (1), p.54-65
• Main Authors: Williams, David L., Ha, Tuanzhu, Li, Chaunfu, Kalbfleisch, John H., Laffan, John J., Ferguson, Donald A.
• Format: Article
• Language: English
• Subjects: Animals; beta-Glucans; Biological and medical sciences; CCAAT-Enhancer-Binding Proteins; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; General aspects; Glucans - therapeutic use; Infection pathogenesis; Infectious diseases; Interleukin-6 - genetics; Male; Medical sciences; Mice; Mice, Inbred ICR; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; RNA, Messenger - analysis; Sepsis - drug therapy; Sepsis - mortality; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1067/msy.1999.99058

Background: Recent data implicate the activation of nuclear factor-κB (NF-κB) and nuclear factor interleukin 6 (NF-IL6) as important steps in the pathophysiologic mechanisms of adult respiratory distress syndrome and systemic inflammatory response syndrome. Methods: This study evaluated the effect of immunomodulating polysaccharides on transcription factor activation, cytokine expression, and mortality in a murine cecal ligation and puncture (CLP) model. ICR/HSD mice were treated with glucan (50 mg/kg) 1 hour before or 15 minutes after CLP. Liver and lung tissue were harvested at 3 hours and mortality trends were observed for 20 days. Results: CLP increased liver and lung NF-κB and NF-IL6 nuclear binding activity as well as tumor necrosis factor-α and interleukin 6 messenger RNA levels at 3 hours. Pretreatment or posttreatment with glucans inhibited tissue NF-κB and NF-IL6 nuclear binding activity and tissue cytokine messenger RNA levels. Prophylaxis with glucan phosphate or scleroglucan increased (P