EFFECTS OF DEXAMETHASONE AND IBUPROFEN ON LPS-INDUCED GENE-EXPRESSIONOF TNF-ALPHA, IL-1-BETA, AND MIP-1-ALPHA IN RAT LUNG

AIM: To study the kinetics of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and macrophage inflammatory protein-1 alpha (MIP-1 alpha) gene expression in rat lung after ip lipopolysacc harides (LPS) and the effect of dexamethasone (Dex) and ibuprofen (Ibu ) on the cytokines gene expression. METHODS: The amount of Evans blue in lung was measured by fluorescence method. The mRNA levels of TNF al pha, IL-1 beta and MIP-1 alpha in rat lung were assessed by slot blot analysis. RESULTS: The mRNA levels of TNF alpha, IL-1 beta, and MIP-1 alpha in rat lung after ip LPS increased in a dose-dependent manner, a nd peaked at 2, 6, and 12 h, respectively. Both Dex 50 mg . kg(-1) and Ibu 90 mg . kg(-1) injected at 1 h before ip LPS markedly decreased t he content of Evans blue in lung at 1 h after ip LPS. After Dex or Ibu pretreatment, the peak levels of TNF alpha, IL-1 beta, and MIP-1 alph a mRNA decreased markedly compared with LPS alone. CONCLUSION: The gen e expression of TNF alpha, IL-1 beta, and MIP-1 alpha in rat lung incr eased after ip LPS. Dex and Ibu prevented LPS-induced lung injury thro ugh inhibiting the cytokines gene expression.