The roles of mTNF-α and sTNF-α in endotoxin shock

Objective To observe the dynamic expression of mTNF α and sTNF α in the development of endotoxin shock and to explore the mechanism of mTNF α in endotoxin shock. Methods Endotoxin shock was induced in rats by intravenous injection of dead gram negative bacteria E.coli ; the kinetics of mTNF α in peritoneal macrophages and sTNF α in serum of these rats were examined. The pretreatment with TACE antisense oligodeoxyribonucleotide(TACE A ODN) (5mg/kg weight) or with polyclonal antibody against TNF α (5mg/kg weight) 30 minutes before injection of dead bacteria inhibited the enzymatic cleavage of mTNF α into sTNF α or neutralizated sTNF α. Six hours after bacteria injection, mTNF α and sTNF α also respectively detected. Pathological injury in lung and kidney in endotoxin shock rats was examined and arteria pressure was measured incessantly. Results The kinetics of mTNF α expression in the development of endotoxin shock was different from that of sTNF α in serum. The expression of mTNF α began to enhance on the surface of peritoneal macrophages in 30 min after the challenge of bacteria and reached the peak within a period of 4.5 hours followed by a gradual decrease to a certain level which was maintained at least 24 hours. TACE A ODN pretreated rats showed a markable increase in mTNF α expression by peritoneal macrophages ( P 0.001) and their arterial blood pressure were maintained in the normal rang and no detectable pathological injury was found in lung and kidney. Pretreat with polyclonal antibody against TNF α led to the similar results with that of the former. Conclusion mTNF α is a potential endogenous regulator involved in antiinflammatory responses to maintain the normal arterial pressure and protect tissue from pathological injury in the process of endotoxin shock. We demonstrated the kinetics of mTNF α expression and its potential effects in endotoxin shock were also reported. [