Role for macrophage migration inhibitory factor in asthma.
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.
Mizue
Y
Y
Yale University School of Medicine, New Haven, CT 06520-8031, USA.
Ghani
S
S
Leng
L
L
McDonald
C
C
Kong
P
P
Baugh
J
J
Lane
S J
SJ
Craft
J
J
Nishihira
J
J
Donnelly
S C
SC
Zhu
Z
Z
Bucala
R
R
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
D016207:Cytokines; D015848:Interleukin-5; D008263:Macrophage Migration-Inhibitory Factors; D010047:Ovalbumin; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse