Am. J. Respir. Crit. Care Med., Volume 160, Number 3, September 1999, 873-878

Interleukin-18 Enhances Antigen-induced Eosinophil Recruitment into the Mouse Airways

KOTARO KUMANO, ATSUHITO NAKAO, HIROSHI NAKAJIMA, FUMIAKI HAYASHI, MASASHI KURIMOTO, HARUKI OKAMURA, YASUSHI SAITO, and ITSUO IWAMOTO

Departments of Medicine II and Physiology II, Chiba University School of Medicine, Chiba; Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama; and Department of Bacteriology, Hyogo College of Medicine, Nishinomiya, Japan

Interleukin-18 (IL-18) has recently been identified as an IFN--inducing factor. Previous studies have shown that CD4⁺ T cells, IL-5, and TNF- mediate, but IFN- and IL-12 (via IFN- production) inhibit antigen-induced eosinophil recruitment into the airways of sensitized mice. Here, we showed that the administration of recombinant murine IL-18 enhanced antigen-induced eosinophil recruitment into the trachea and bronchoalveolar lavage fluids (BALF) of sensitized mice in a dose-dependent manner. The administration of IL-18 enhanced antigen-induced IFN- and TNF- production, but not IL-5 production, in the BALF and lungs of sensitized mice. Neutralizing antibody against TNF- prevented antigen-induced eosinophil recruitment into the BALF of sensitized mice. Although IL-18 enhanced antigen-induced airway eosinophilia, IL-18 did not affect antigen-induced airway hyperresponsiveness in sensitized mice. These results indicate that IL-18, unlike IFN- and IL-12, enhances antigen-induced eosinophil recruitment into the airways in part by increasing antigen-induced TNF- production of sensitized animals. These findings suggest that IL-18 may contribute to the development and exacerbation of airway inflammation in asthma.

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