Interleukin-18 enhances antigen-induced eosinophil recruitment into the mouse airways.
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.
Kumano
K
K
Departments of Medicine II and Physiology II, Chiba University School of Medicine, Chiba, Japan.
Nakao
A
A
Nakajima
H
H
Hayashi
F
F
Kurimoto
M
M
Okamura
H
H
Saito
Y
Y
Iwamoto
I
I
D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000187:drug effects* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000276:immunology / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000941:Antigens; D020382:Interleukin-18; D015848:Interleukin-5; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma