Flt3 ligand: a novel cytokine prevents allergic asthma in a mouse model.
Flt-3 ligand (FL), a recently described growth factor affecting early hematopoietic progenitor cells, can also support the expansion of dendritic cells secreting IL-12. Since type 2 T cells predominate in asthma and IL-12 prevents the differentiation of naive T lymphocytes to a type 2 phenotype, we hypothesized that FL could prevent the development of asthma-like conditions in the ovalbumin mouse model. We found that co-administration of FL during ovalbumin sensitization abrogated late allergic responses, but had no effect on early allergic responses. Airway hyperresponsiveness to methacholine was also blocked by FL treatment. Analysis of bronchoalveolar lavage (BAL) fluid demonstrated a significant reduction in eosinophils, with concomitant decreases in IL-5 and increases in IFN-gamma levels. However, there was no change in BAL fluid IL-4 and serum IgE levels. These data suggest that FL treatment prevents ovalbumin-induced asthma in the mouse and may provide a useful adjuvant in the treatment of human asthma.
Agrawal
D K
DK
Center for Allergy, Asthma and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA. dkagr@creighton.edu
Hopfenspirger
M T
MT
Chavez
J
J
Talmadge
J E
JE
D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000378:metabolism*; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D008565:Membrane Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D011657:Pulmonary Eosinophilia / Q000517:prevention & control; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D015848:Interleukin-5; D008565:Membrane Proteins; C084881:flt3 ligand protein; D016210:Methacholine Chloride; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin