Role of CXC chemokines in the enhancement of LPS-induced neutrophil accumulation in the lung of mice by dexamethasone

Lipopolysaccharide (LPS)-induced multiple organ injury was mediated in part by a transcription factor, nuclear factor-κB (NF-κB). Mice were pretreated with dexamethasone (DEX), an inhibitor of NF-κB activation, to elucidate its effects on LPS-induced early responses in vivo. Early responses measured 1 h after intraperitoneal LPS administration at a dose of 1 mg/kg were (1) neutrophil accumulation in the tissues, (2) neutrophil degranulation, and (3) protein and mRNA expressions of tumor necrosis factor-α (TNF-α) and ELR + CXC chemokines [macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (KC)]. Treatment with DEX before LPS administration suppressed NF-κB activation and plasma TNF-α levels almost to undetectable levels, but enhanced neutrophil accumulation and augmented MIP-2 levels in the lung. The suppression of plasma TNF-α levels by pretreatment with an anti-TNF-α antibody did not enhance LPS-induced neutrophil accumulation in the lung. These results demonstrate that the enhancement of LPS-induced neutrophil accumulation by DEX might be mediated by MIP-2 and not by TNF-α.