• Li Gao, Carlos Flores, Shwu Fan-Ma, Edmund J Miller, Jaideep Moitra, Liliana Moreno, Raj Wadgaonkar, Brett Simon, Roy Brower, Jonathan Sevransky, Rubin M Tuder, James P Maloney, Marc Moss, Carl Shanholtz, C Ryan Yates, Gianfranco Umberto Meduri, Shui Q Ye, Kathleen C Barnes, and Joe G N Garcia.
• Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
• Transl Res. 2007 Jul 1; 150 (1): 182918-29.

AbstractThe macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine central to the response to endotoxemia, is a putative biomarker in acute lung injury (ALI). To explore MIF as a molecular target and candidate gene in ALI, the MIF gene and protein expression were examined in murine and canine models of ALI (high tidal volume mechanical ventilation, endotoxin exposure) and in patients with either sepsis or sepsis-induced ALI. MIF gene expression and protein levels were significantly increased in each ALI model, with serum MIF levels significantly higher in patients with either sepsis or ALI compared with healthy controls (African- and European-descent). The association of 8 MIF gene polymorphisms (single-nucleotide polymorphisms (SNPs)) (within a 9.7-kb interval on chromosome 22q11.23) with the development of sepsis and ALI in European-descent and African-descent populations was studied next. Genotyping in 506 DNA samples (sepsis patients, sepsis-associated ALI patients, and healthy controls) revealed haplotypes located in the 3' end of the MIF gene, but not individual SNPs, associated with sepsis and ALI in both populations. These data, generated via functional genomic and genetic approaches, suggest that MIF is a relevant molecular target in ALI.

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