Relationship between cytokine mRNA expression and organ damage following cecal ligation and puncture.

aimTo investigate the role of cytokine gene expression in organ damage at different tissue sites during sepsis.

methodsMale NIH mice were subjected to cecal ligation and puncture (CLP) or sham operation (Sham). Pro-inflammatory cytokine (TNFalpha, IL-1beta and IL-6) and anti-inflammatory cytokine (IL-4) gene expression in the liver and lung tissue were assessed by RT-PCR. The permeability of microvascular and water content in the lungs and liver were also examined.

resultsSignificant increase in TNFalpha, IL-1beta and IL-6 gene expression was observed at 3 and 12 h after CLP both in the liver and lungs (P<0.01).The level of IL-4 gene expression was not changed after CLP in the lungs, but increased at 12 h after CLP(P<0.01) in the liver tissue. Both the liver and lungs showed a significant increase in microcirculatory permeability at 12 h after CLP(P<0.01), and the increase in the lungs was higher than that in the liver. The water mass fractions in the liver (P<0.05) and lungs (P<0.01) were increased after CLP, and the increase in the lungs happened earlier and more severely than that in the liver.

conclusionThe inflammatory response in the liver and lungs was different during sepsis. At the early stage of sepsis, pro-inflammatory reaction dominates both in the liver and lungs. But at the later stage of sepsis, induction of compensatory anti-inflammatory response was seen in the liver but not in the lungs. This difference in situ activity may contribute to the different vulnerability of organ damage during sepsis. The strategy of systemic administration of anti-inflammatory drugs to sepsis should be reconsidered.