IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2.

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.

• Authors: K Blease, S L Kunkel, C M Hogaboam
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 50 Issue 11 Pg. 552-60 (Nov 2001) ISSN: 1023-3830 [Print] Switzerland
• PMID: 11766995 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ccl11 protein, mouse
• Chemokine CCL11
• Chemokine CXCL2
• Chemokines
• Chemokines, CC
• Cxcl2 protein, mouse
• Drosophila Proteins
• Interleukin-18
• Membrane Glycoproteins
• RNA, Messenger
• Receptors, Cell Surface
• Toll-Like Receptor 2
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• Aspergillus fumigatus (immunology, isolation & purification)
• Asthma (prevention & control)
• Bronchial Hyperreactivity (etiology)
• Chemokine CCL11
• Chemokine CXCL2
• Chemokines (biosynthesis)
• Chemokines, CC (biosynthesis)
• Chronic Disease
• Drosophila Proteins
• Eosinophils (physiology)
• Female
• Interferon-gamma (analysis)
• Interleukin-12 (analysis)
• Interleukin-18 (analysis, physiology)
• Lung (metabolism, microbiology)
• Membrane Glycoproteins (genetics, physiology)
• Mice
• Mice, Inbred CBA
• Neutrophils (physiology)
• RNA, Messenger (analysis)
• Receptors, Cell Surface (genetics, physiology)
• Toll-Like Receptor 2
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha (biosynthesis)