Potential protective effect of NF-kappa B activity on the polymicrobial sepsis of rats preconditioning heat shock treatment

The present study was designed to investigate the role of NF-kappaB in infl uencing the outcome of sepsis modulated by previous heat shock treatment. S epsis was induced in rats by cecum ligation and puncture (CLP) method, whic h 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 ear ly 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 init iated during early sepsis and apparently suppressed during late stage of se psis. 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 lat e sepsis could be attenuated by pretreatment of heat shook through the pres ervation of p65 expression. The results may provide a mechanistic explanati on for the improved outcome to polymicrobial sepsis of rats that are precon ditioned with heat shock, as well as a novel highlight for therapeutic inte rvention of severe infection. (C) 2000 Elsevier Science B.V. All rights res erved.