GENETIC COMPONENT IN THE INFLAMMATORY RESPONSE INDUCED BY BACTERIAL LIPOPOLYSACCHARIDE

Multiple organ dysfunction syndrome (MODS) appears to be the result of a complex program influenced by multiple factors, including environme ntal, physiological, and immunological conditions. Thus, an uncontroll ed inflammatory response following a stochastic event, the initial inj ury, is believed to be the cause for the development of this syndrome. Several lines of evidence suggest that a genetic component could cont ribute to the regulation of the inflammatory response, as well, but no direct evidence demonstrates a heritable predisposition to MODS. in t he present study, a genetic contribution was demonstrated for the infl ammatory response induced by the administration of bacterial lipopolys accharide (LPS) in different, genetically distinct strains of inbred m ice. A survey of five inbred strains showed that mortality following a dministration of Escherichia coil LPS (20 mg/kg) was highest in C57BL/ 6J (B6) mice, while A/J mice were the most resistant. Accordingly, B6 and A/J mice were examined further for differences in the inflammatory response elicited by LPS. B6 mice showed higher levels of circulating interleukin-1 beta and interleukin-6, as well as higher mRNA levels o f hepatic beta-fibrinogen (an acute-phase gene) and metallothionein. S urprisingly, the circulating levels of tumor necrosis factor-alpha wer e significantly higher in A/J than in B6 mice after LPS administration . Since B6 and A/J mice were bred and raised in identical environments and received the same LPS challenge, the contrasting inflammatory res ponse that was observed is largely attributable to genetic differences between these two strains. These data illustrate that the response to injury could be modulated by the genetic background of the individual . This information may be pertinent for the care of critically ill pat ients.