title: Role for macrophage migration inhibitory factor in asthma.
abstract: Macrophage migration inhibitory factor (MIF) is an immunologic regulator that is expressed in inflammatory and autoimmune disorders. We investigated MIF's role in asthma using genetic approaches in a mouse model and in a cohort of asthma patients. Mice genetically deficient in MIF that were primed and aerosol-challenged with ovalbumin showed less pulmonary inflammation and lower airway hyperresponsiveness than genetically matched, wild-type controls. MIF deficiency also resulted in lower titers of specific IgE, IgG(1), and IgG(2a), and decreased pulmonary, T(H)2 cytokine levels. IL-5 concentrations were lower and corresponded to decreased eosinophil numbers in bronchoalveolar lavage fluid. T cell studies also showed a lower level of antigen-specific responses in MIF-KO versus wild-type mice. In an analysis of 151 white patients with mild, moderate, or severe asthma (Global Initiative for Asthma criteria), a significant association was found between mild asthma and the low-expression, 5-CATT MIF allele. Pharmacologic inhibition of MIF may be beneficial and could be guided by the MIF genotype of affected individuals.
authors.affiliation: Yale University School of Medicine, New Haven, CT 06520-8031, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Mizue
authors.forename: S
authors.initials: S
authors.lastname: Ghani
authors.forename: L
authors.initials: L
authors.lastname: Leng
authors.forename: C
authors.initials: C
authors.lastname: McDonald
authors.forename: P
authors.initials: P
authors.lastname: Kong
authors.forename: J
authors.initials: J
authors.lastname: Baugh
authors.forename: S J
authors.initials: SJ
authors.lastname: Lane
authors.forename: J
authors.initials: J
authors.lastname: Craft
authors.forename: J
authors.initials: J
authors.lastname: Nishihira
authors.forename: S C
authors.initials: SC
authors.lastname: Donnelly
authors.forename: Z
authors.initials: Z
authors.lastname: Zhu
authors.forename: R
authors.initials: R
authors.lastname: Bucala
mesh_terms: D000328:Adult; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D018893:Bronchoalveolar Lavage; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D040461:Gene Components; D005838:Genotype; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D019746:Intramolecular Oxidoreductases; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
chemical_list: D016207:Cytokines; D015848:Interleukin-5; D008263:Macrophage Migration-Inhibitory Factors; D010047:Ovalbumin; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse