Expression of TNF alpha, IL-1 beta, IL-6 mRNA, release of TNF alpha in vital organs and their relationship with endotoxin translocation following hemorrhagic shock.

This study was designed to systematically investigate expression of TNF alpha, IL-1 beta, Il-6 mRNA in the liver, lungs and kidneys, release of TNF alpha in the above tissues, their relationship with hepatic, pulmonary and renal dysfunction, and distribution of endogenous endotoxin in tissues after hemorrhagic shock in mice and rats, with reverse-transcription-polymerase chain reaction, ELISA, etc, to elucidate the kinetics of expression and release of major cytokines in vital organs, their role and mechanism of production in shock. The results were: 1. expression of TNF alpha, IL-1 beta, IL-6 mRNA in vital organs successively increased after hemorrhagic shock and resuscitation, and TNF alpha expression was the first to appear followed by IL-1 beta. Though expression of IL-6 mRNA appeared late, it persisted longer; 2. TNF alpha levels in the liver, lungs and kidneys were all elevated but to different degrees after shock and resuscitation. At 3 hours after resuscitation, TNF alpha levels in the three above tissues were still significantly high, while plasma TNF alpha levels were already decreased to control levels; 3. hepatic, pulmonary and renal functions were damaged to different degrees after hemorrhagic shock, with hepatic dysfunction being the most severe; 4. endotoxin levels in the liver, lungs and kidneys were markedly increased after shock and resuscitation, and paralleled the expression of cytokine genes. In addition, there was significant correlation between changes in endotoxin level in tissues and TNF alpha release in tissues during early shock. It is suggested that expression and release of cytokines in vital organs might play an important role in local organ damage after hemorrhagic shock, and production of cytokines is related to endotoxin translocation.