RATIONALE: Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. It contributes toward an exaggerated gram-negative inflammatory response via its ability to induce Toll-like receptor-4 expression. Studies have shown that MIF knockout mice have less aggressive Pseudomonas infection (compared with wild-type). OBJECTIVES: To assess whether a novel functional MIF polymorphism was associated with clinical prognosis in a patient cohort with chronic gram-negative infection, namely cystic fibrosis (CF). METHODS: Collected genomic DNA was analyzed via polymerase chain reaction amplification for the polymorphic region for the CATT repeat polymorphism. Individuals may have a 5-, 6-, 7-, or 8-CATT tetranucleotide repeat unit on each allele. The 5-CATT repeat allele exhibits the lowest MIF promoter activity. MEASUREMENTS AND MAIN RESULTS: Patients with stable CF (n = 167) and a matched control group (n = 166) were enrolled. In patients with CF, the MIF5(+) group had a decreased incidence of Pseudomonas aeruginosa colonization (odds ratio, 0.25; 95% confidence interval, 0.09-0.65; p = 0.004) and a significant reduction in the risk of pancreatic insufficiency (odds ratio, 0.27; 95% confidence interval, 0.07-1.0; p = 0.05). A trend toward milder disease activity in the MIF5(+) group was seen with all other parameters. CONCLUSIONS: The results support the concept of a regulatory role for MIF in CF.
RATIONALE: Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator. It contributes toward an exaggerated gram-negative inflammatory response via its ability to induce Toll-like receptor-4 expression. Studies have shown that MIF knockout mice have less aggressive Pseudomonas infection (compared with wild-type). OBJECTIVES: To assess whether a novel functional MIF polymorphism was associated with clinical prognosis in a patient cohort with chronic gram-negative infection, namely cystic fibrosis (CF). METHODS: Collected genomic DNA was analyzed via polymerase chain reaction amplification for the polymorphic region for the CATT repeat polymorphism. Individuals may have a 5-, 6-, 7-, or 8-CATT tetranucleotide repeat unit on each allele. The 5-CATT repeat allele exhibits the lowest MIF promoter activity. MEASUREMENTS AND MAIN RESULTS:Patients with stable CF (n = 167) and a matched control group (n = 166) were enrolled. In patients with CF, the MIF5(+) group had a decreased incidence of Pseudomonas aeruginosa colonization (odds ratio, 0.25; 95% confidence interval, 0.09-0.65; p = 0.004) and a significant reduction in the risk of pancreatic insufficiency (odds ratio, 0.27; 95% confidence interval, 0.07-1.0; p = 0.05). A trend toward milder disease activity in the MIF5(+) group was seen with all other parameters. CONCLUSIONS: The results support the concept of a regulatory role for MIF in CF.
Authors: Huzaifa Adamali; Michelle E Armstrong; Anne Marie McLaughlin; Gordon Cooke; Edward McKone; Christine M Costello; Charles G Gallagher; Lin Leng; John A Baugh; Günter Fingerle-Rowson; Richard J Bucala; Paul McLoughlin; Seamas C Donnelly Journal: Am J Respir Crit Care Med Date: 2012-05-16 Impact factor: 21.405
Authors: Leona Mawhinney; Michelle E Armstrong; Ciaran O' Reilly; Richard Bucala; Lin Leng; Gunter Fingerle-Rowson; Darren Fayne; Michael P Keane; Aisling Tynan; Lewena Maher; Gordon Cooke; David Lloyd; Helen Conroy; Seamas C Donnelly Journal: Mol Med Date: 2015-04-16 Impact factor: 6.354
Authors: Sarah Doernberg; Bernhard Schaaf; Klaus Dalhoff; Lin Leng; Anna Beitin; Vincent Quagliarello; Richard Bucala Journal: Cytokine Date: 2011-01-03 Impact factor: 3.861
Authors: Dake Qi; Xiaoyue Hu; Xiaohong Wu; Melanie Merk; Lin Leng; Richard Bucala; Lawrence H Young Journal: J Clin Invest Date: 2009-11-16 Impact factor: 14.808