[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.


CONCLUSIONS
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.
Qiu
H
H
Department of Critical Care Medicine, Peking Union Medical College, Beijing.
Pan
J
J
Zhao
Y
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D054407:Chemokine CCL4; D003907:Dexamethasone / Q000494:pharmacology; D004926:Escherichia coli; D015870:Gene Expression; D007052:Ibuprofen / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054407:Chemokine CCL4; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007052:Ibuprofen