Inhibiting early activation of tissue nuclear factor-kappa B and nuclear factor interleukin 6 with (1 -> 3)-beta-D-glucan increases long-term survival in polymicrobial sepsis

Background. Recent data implicate the activation of nuclear factor-kappa B (NF-KB) and nuclear factor interleukin 6 (NF-IL6) as important steps in the pathophysiologic mechanisms of adult respiratory distress syndrome and sys temic inflammatory response syndrome. Methods. This study evaluated the effect of immunomodulating polysaccharide s on transcription factor activation, cytokine expression, and mortality in a murine cecal ligation and puncture (CLP) model. ICR/HSD mice were treate d with glucan (50 mg/kg) 1 hour before or 15 minutes after CLP. Liver and l ung tissue were harvested at 3 hours and mortality trends were observed for 20 days. Results. CLP increased liver and lung NF-kappa B and NF-IL6 nuclear binding activity as well as tumor necrosis factor-alpha and interleukin 6 messenge r RNA levels at 3 hours. Pretreatment or posttreatment with glucans inhibit ed tissue NF-kappa B and NF-IL6 nuclear binding activity and tissue cytokin e messenger RNA levels. Prophylaxis with glucan phosphate or scleroglucan i ncreased (P <.001) long-term survival (20% CLP vs 65 glucan phosphate, 75% scleroglucan). Posttreatment with glucan phosphate also increased (P <.05) long-term survival (20% vs 65%). Conclusions. Pretreatment or posttreatment with biologic response modifiers decreased tissue transcription factor nuclear binding activity and cytokin e message in liver and lung of septic mice. Inhibiting early transcription factor activation and cytokine message expression correlates with improved outcome in polymicrobial sepsis as denoted by increased long-term survival.