Cystic fibrosis, disease severity, and a macrophage migration inhibitory factor polymorphism
American journal of respiratory and critical care medicine, 2005•atsjournals.org
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 …
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 …
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.
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