Ž . International Immunopharmacology 1 2001 2081–2089 www.elsevier.comrlocaterintimp Flt3 ligand: a novel cytokine prevents allergic asthma in a mouse model Devendra K. Agrawal a, ) , Michael T. Hopfenspirger a , Jennifer Chavez b , James E. Talmadge b a Center for Allergy, Asthma and Immunology, Creighton UniÕersity School of Medicine, Omaha, NE 68178, USA b Department of Pathology and Microbiology, UniÕersity of Nebraska Medical Center, Omaha, NE 68198, USA Received 4 May 2001; received in revised form 18 June 2001; accepted 25 June 2001 Abstract Ž . 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 Ž . 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-g 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. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Airway hyperresponsiveness; Asthma; Eosinophilia; Flt-3 ligand; Late allergic response 1. Introduction Regulation of the type 1 T cell response as it relates to allergy and asthma has been suggested to modulate the immune response to the sensitizing antigen and to suppress disease associated type 2 T w x cell responses 1–3 . These studies focused on stimu- lating type 1 responses, as the type 1 subset has been wx shown to be antagonistic to type 2 response 4 . The ) Corresponding author. Departments of Medicine, Medical Microbiology and Immunology, Creighton University School of Medicine, CRISS I Room 131 2500 California Plaza Omaha, NE 68178, USA. Tel.: q 1-402-280-2938; fax: q 1-402-280-1843. Ž . E-mail address: dkagr@creighton.edu D.K. Agrawal . mycobacterial antigens of Bacillus Calmette–Guerin Ž . wx BCG , which can up-regulate a type 1 response 5 , have shown therapeutic activity for allergen-induced w x asthma in both experimental animal models 6,7 and wx in clinical studies 8 . More recently, attention has focused on the unmethylated CpG DNA motif that was thought to be at least partially responsible for the immunogenic properties of BCG and its ability to w x activate type 1 cytokine production 9,10 . The draw- Ž backs for mycobacteria may include but are not . limited to latent infection, loss of delayed-type hy- persensitivity skin testing for mycobacterial infec- tion, and in the case of CpG, potential production of autoreactive antibodies or the induction of cytotoxic w x shock 10 . 1567-5769r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. Ž . PII: S1567-5769 01 00122-9