Role for macrophage migration inhibitory factor in asthma

Y. Mizue, S. Ghani, L. Leng, C. McDonald, P. Kong, J. Baugh, S. J. Lane, J. Craft, J. Nishihira, S. C. Donnelly, Z. Zhu, R. Bucala

Research output: Contribution to journalArticle

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, IgG1, and IgG2a, and decreased pulmonary, TH2 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.

Original languageEnglish (US)
Pages (from-to)14410-14415
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number40
DOIs
StatePublished - Oct 4 2005
Externally publishedYes

Keywords

  • Cytokine
  • Genetic polymorphism
  • Innate immunity

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Role for macrophage migration inhibitory factor in asthma'. Together they form a unique fingerprint.

  • Cite this

    Mizue, Y., Ghani, S., Leng, L., McDonald, C., Kong, P., Baugh, J., Lane, S. J., Craft, J., Nishihira, J., Donnelly, S. C., Zhu, Z., & Bucala, R. (2005). Role for macrophage migration inhibitory factor in asthma. Proceedings of the National Academy of Sciences of the United States of America, 102(40), 14410-14415. https://doi.org/10.1073/pnas.0507189102