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Published on: July 7, 2017
IL-18 deficiency selectively enhances allergen-induced eosinophilia in mice
T Kodama1, T Matsuyama, K Kuribayashi
1Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
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.
