[The role of TNF alpha, IL-1 beta and MIP-1 alpha in LPS-induced organ injury].

OBJECTIVE

To investigate the role of inflammatory cytokines in endotoxemia models and to explore the possible anti-cytokine therapy of endotoxemia.

METHODS

TNF alpha in plasma was measured by ELISA, and the mRNA of cytokines was assessed by slot blot analysis.

RESULTS

LPS-induced TNF alpha release was in a dose:dependent manner in human whole blood. Dexamethasone (> or = 10(-8)mol/L) exhibited inhibitory effect on TNFa release. Ibuprofen 10(-7)-10(-9) mol/L had inhibitory effect on TNFa production, whereas 10(-3)-10(-4)mol/L stimulated TNFa release. The rat model of acute lung injury was made by LPS intraperitoneal injection. Both dexamethasone and ibuprofen that injected at 1 hour before LPS injection could decrease the contents of Evans blue in the lung (t 2.80 and 7.31 respectively, P < 0.05 vs LPS control). After LPS administered, there was a progressive up regulation in transcripts of TNF alpha, IL-1 beta and MIP-1 alpha in whole lung homogenates of rats. The mRNA peaked at 2, 6, 12 hours respectively. The TNF alpha, IL-1 beta and MIP-1 alpha mRNA levels decreased markedly when dexamethasone or ibuprofen given at 1 hour before LPS injection.

CONCLUSION

TNF alpha, IL-1 beta and MIP-1 alpha play an essential role in the inflammatory response. LPS-induced acute lung injury may be prevented by dexamethasone and ibuprofen which have inhibitory effect on the gene expression of cytokines in the lung.