IL-18 deficiency selectively enhances allergen-induced eosinophilia in mice.

Abstract

BACKGROUND:

T(H2) cytokines are associated with airway inflammation and hyperreactivity in bronchial asthma, and restoration of the T(H1)/T(H2) imbalance is a potential avenue for novel therapies. IL-18 is a cytokine secreted by activated macrophages, and it shares some of its biologic activities with IL-12, a typical T(H1)-type cytokine. Although IL-18 and IL-12 act on T cells synergistically to induce IFN-gamma production, the contribution of IL-18 T(H1)/T(H2) imbalance and to subsequent asthmatic response has not been elucidated in vivo.

OBJECTIVE:

We studied a model of allergic asthma in IL-18-deficient mice to investigate the modulatory role of IL-18 on induction and maintenance of T(H2) mucosal immunity. We also have investigated the ability of intraperitoneal instilled IL-18 to reduce T(H2) mucosal immunity in IL-18-deficient mice.

METHODS:

IL-18-deficient mice immunized to ovalbumin by means of intraperitoneal injection were challenged 3 times with an aerosol of ovalbumin every second day for 8 days. Recombinant (r)IL-18 was intraperitoneally administered in mice before every first challenge. Mice were analyzed for effects on lung eosinophilia, cytokines, and serum IgE levels.

RESULTS:

In IL-18-deficient mice, levels of eosinophilia and lung damage were significantly higher than in wild-type C57/BL6 litter mates. Intraperitoneal administration of rIL-18 in deficient mice reduced these antigen-induced changes to levels seen in wild-type mice in association with a decrease in IL-4 in bronchoalveolar lavage fluid and lung tissue. However, administration of rIL-18 did not affect the IFN-gamma level and somewhat enhanced the production of IL-5. Notably, reconstitution with rIL-18 increased the numbers of cells staining for Fas ligand, as well as apoptotic cells stained by nick end-labeling in bronchial submucosa infiltrates.

CONCLUSION:

These findings indicate that in vivo IL-18 not only inhibited antigen-specific T(H2) development but also affected apoptosis through Fas-Fas ligand interactions. These data support a role for IL-18 in the complex pathogenesis of allergic inflammation in which IL-18 limited the development of the local inflammatory response to antigen.

• Authors: T Kodama, T Matsuyama, K Kuribayashi, Y Nishioka, M Sugita, S Akira, K Nakanishi, H Okamura
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 105 Issue 1 Pt 1 Pg. 45-53 (Jan 2000) ISSN: 0091-6749 [Print] United States
• PMID: 10629451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Cytokines
• Interleukin-18
• Recombinant Proteins
• Immunoglobulin E

Topics

• Allergens (immunology)
• Animals
• Apoptosis (drug effects)
• Asthma (immunology, physiopathology)
• Bronchial Hyperreactivity (immunology)
• Cytokines (metabolism)
• Eosinophilia (immunology, pathology, physiopathology)
• Immunoglobulin E (metabolism)
• Interleukin-18 (deficiency, pharmacology)
• Lung (drug effects, metabolism, pathology, physiopathology)
• Male
• Mice
• Mice, Inbred C57BL
• Recombinant Proteins (pharmacology)