Role for macrophage migration inhibitory factor in asthma

Autor: John A. Baugh, Lin Leng, Courtney McDonald, Zhou Zhu, Seamas C. Donnelly, Yuka Mizue, Joe Craft, J. Nishihira, S. Ghani, Richard Bucala, S. J. Lane, Philip Kong
Rok vydání: 2005
Předmět:
Zdroj: Proceedings of the National Academy of Sciences. 102:14410-14415
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.0507189102
Popis: 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.
Databáze: OpenAIRE