title: Functional polymorphisms in the gene encoding macrophage migration inhibitory factor are associated with Gram-negative bacteremia in older adults.
abstract: Macrophage migration inhibitory factor (MIF) is an immune mediator encoded in a functionally polymorphic locus. We found the genotype conferring low expression of MIF to be enriched in a cohort of 180 patients with gram-negative bacteremia, compared with 229 healthy controls (odds ratio [OR], 2.4; P = .04), an association that was more pronounced in older adults (OR, 4.6; P = .01). Among older subjects, those with low expression of MIF demonstrated 20% reduced MIF production from lipopolysaccharide-stimulated peripheral blood monocytes and 30% lower monocyte surface Toll-like receptor 4, compared with those with high expression. Our work suggests that older adults with low expression of MIF may be predisposed to hyporesponsiveness to lipopolysaccharide and gram-negative bacterial infection.
authors.affiliation: Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Das
authors.forename: Lakshman
authors.initials: L
authors.lastname: Subrahmanyan
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
authors.forename: David
authors.initials: D
authors.lastname: van Duin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Levy
authors.forename: Marta
authors.initials: M
authors.lastname: Piecychna
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Montgomery
authors.forename: Albert
authors.initials: A
authors.lastname: Shaw
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
mesh_terms: D016470:Bacteremia / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006090:Gram-Negative Bacteria / Q000378:metabolism; D016905:Gram-Negative Bacterial Infections / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: MIF; gram-negative infection; immune response; macrophage