Interleukin-18 Enhances Antigen-Induced Eosinophil Recruitment Into the Mouse Airways

Am J Respir Crit Care Med. 1999 Sep;160(3):873-8. doi: 10.1164/ajrccm.160.3.9805026.

Abstract

Interleukin-18 (IL-18) has recently been identified as an IFN-gamma-inducing factor. Previous studies have shown that CD4(+) T cells, IL-5, and TNF-alpha mediate, but IFN-gamma and IL-12 (via IFN-gamma 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-gamma and TNF-alpha production, but not IL-5 production, in the BALF and lungs of sensitized mice. Neutralizing antibody against TNF-alpha 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-gamma and IL-12, enhances antigen-induced eosinophil recruitment into the airways in part by increasing antigen-induced TNF-alpha production of sensitized animals. These findings suggest that IL-18 may contribute to the development and exacerbation of airway inflammation in asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antigens / drug effects*
  • Antigens / immunology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Eosinophils / drug effects*
  • Eosinophils / immunology
  • Female
  • Interferon-gamma / biosynthesis
  • Interleukin-18 / immunology
  • Interleukin-18 / pharmacology*
  • Interleukin-5 / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Trachea / drug effects*
  • Trachea / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antigens
  • Interleukin-18
  • Interleukin-5
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma