K Blease1, S L Kunkel, C M Hogaboam. 1. Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Abstract
UNLABELLED: Fungus-induced asthmatic disease is characterized by persistent airway hyperreactivity and remodeling. OBJECTIVE AND DESIGN: To determine the role of IL-18 in the allergic airway response to Aspergillus fumigatus conidia in a murine model of A. fumigatus-induced asthma. METHODS: A. fumigatus-sensitized mice were depleted of IL-18 using a polyclonal anti-IL-18 antibody for 3 days after a conidia challenge. RESULTS: Airway hyperresponsiveness and eosinophil numbers were significantly elevated 3-30 days after conidia challenge compared to the normal serum-treated group. Histological evidence showed retention of A. fumigatus conidia, airway remodeling, subepithelial fibrosis, and increased collagen deposition in the lungs of IL-18-depleted mice at day 30 after the conidia challenge. Prolonged retention of conidia in IL-18 depleted A. fumigatus-sensitized mice was associated with decreased Toll-like receptor-2 (TLR-2) expression compared with the control group. CONCLUSIONS: IL-18 modulates the innate immune response against A. fumigatus conidia and prevents the development of severe fungus-induced asthmatic disease.
UNLABELLED: Fungus-induced asthmatic disease is characterized by persistent airway hyperreactivity and remodeling. OBJECTIVE AND DESIGN: To determine the role of IL-18 in the allergic airway response to Aspergillus fumigatus conidia in a murine model of A. fumigatus-induced asthma. METHODS:A. fumigatus-sensitized mice were depleted of IL-18 using a polyclonal anti-IL-18 antibody for 3 days after a conidia challenge. RESULTS:Airway hyperresponsiveness and eosinophil numbers were significantly elevated 3-30 days after conidia challenge compared to the normal serum-treated group. Histological evidence showed retention of A. fumigatus conidia, airway remodeling, subepithelial fibrosis, and increased collagen deposition in the lungs of IL-18-depleted mice at day 30 after the conidia challenge. Prolonged retention of conidia in IL-18 depleted A. fumigatus-sensitized mice was associated with decreased Toll-like receptor-2 (TLR-2) expression compared with the control group. CONCLUSIONS:IL-18 modulates the innate immune response against A. fumigatus conidia and prevents the development of severe fungus-induced asthmatic disease.
Authors: Kristin J Carpenter; Jillian L Ewing; Jane M Schuh; Traci L Ness; Steven L Kunkel; Monica Aparici; Montserrat Miralpeix; Cory M Hogaboam Journal: Br J Pharmacol Date: 2005-08 Impact factor: 8.739