Potential protective effect of NF-kappaB activity on the polymicrobial sepsis of rats preconditioning heat shock...

The present study was designed to investigate the role of NF-kappaB in influencing the outcome of sepsis modulated by previous heat shock treatment. Sepsis was induced in rats by cecum ligation and puncture (CLP) method, which manifests two distinct clinical phases: an initial hyperdynamic phase (9 h after CLP, early sepsis) followed by a hypodynamic phase (18 h after CLP, late sepsis). Rats of heated group were treated by whole body hyperthermia 24 h prior to the CLP operation. Lymphocytes were collected during the early and late sepsis phases. The expressions of Hsp72, p65 and I-kappa B were evaluated by Western blot and immunochemical analysis. NF-kappaB activity was detected by EMSA. The results showed that NF-kappaB activation was initiated during early sepsis and apparently suppressed during late stage of sepsis. Previously treated by heat shock, late-sepsis rats emerged with high preservation of p65 expression and NF-kappaB activity, while Hsp72 was over-expressed. In conclusion, down-regulation of NF-kappaB activity during late sepsis could be attenuated by pretreatment of heat shock through the preservation of p65 expression. The results may provide a mechanistic explanation for the improved outcome to polymicrobial sepsis of rats that are preconditioned with heat shock, as well as a novel highlight for therapeutic intervention of severe infection.