Early activation of pulmonary nuclear factor kappa B and nuclear factor interleukin-6 in polymicrobial sepsis

Background: Transcription factor activation may be a pivotal step in the pa thophysiology of sepsis syndrome and adult respiratory distress syndrome. T his study investigated the activation of lung nuclear factor kappa B (NF ka ppa B) and nuclear factor interleukin-6 (NF-IL6:) and how they correlate to proinflammatory cytokine expression and mortality in a murine model of cec al ligation and puncture (CLP), Methods: Polymicrobial sepsis was induced by CLP, Transcription factor acti vation was assessed at 0, 1, 2, 3, 4, 5, 6, 8, and 24 hours after CLP by th e electrophoretic mobility-shift assay, Lung cytokine mRNA levels were esta blished by reverse transcriptase-polymerase chain reaction, Results: CLP induced pulmonary NF kappa B activation at 3, 4. and 8 hours ( p < 0.05). Lung NF kappa B activation peaked at 3 hours (533% vs. no surger y, 2,900% vs. sham treatment) after CLP, Supershift analysis revealed a pre dominance of p50 subunits in the lung nuclear extracts of septic mice 3 hou rs after CLP, indicating the presence of p50 homodimer, In contrast, liver nuclear extracts from septic mice indicated the presence of both p65 and p5 0 subunits at 3 hours, Lung NF-IL6 activation (p < 0.05) was observed at 4 hours (649% vs. no surgery, 296% vs, sham treatment) and 6 hours after CLP. Lung tumor necrosis factor-alpha mRNA levels were increased (p < 0.05) at all time interval after CLP. Lung IL-6 mRNA levels were increased at 3, 6, and 8 hours after CLP. Conclusion: Early activation of lung NF kappa B and NF-IL6 and lung cytokin e mRNA expression correlated with mortality in polymicrobial sepsis. Althou gh IL-6 mRNA levels correlated with NF kappa B and NF-IL6 activation, tumor necrosis factor-alpha mRNA levels did not, in that they preceded transcrip tion factor activation, These data suggest a potential role for NF kappa B and NF-IL6 activation in the initiation and propagation of acute lung injur y.