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Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse.

Sugimoto T, Ishikawa Y, Yoshimoto T, Hayashi N, Fujimoto J, Nakanishi K - J. Exp. Med. (2004)

Bottom Line: Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18.Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro.Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, 663-8501, Japan.

ABSTRACT
Interleukin (IL)-18 was originally regarded to induce T helper cell (Th)1-related cytokines. In general, factors favoring interferon (IFN)-gamma production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid a background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their role in induction of bronchial asthma. Administration of antigen (Ag) induced both airway inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, the same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were coadministered with IL-18. Furthermore, mice having received IFN-gamma-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR after intranasal administration of Ag and IL-18. Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

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Effect of the IL-13 blockage on IL-18 induced AHR and eosinophilia in mice receiving memory Th1 cells. 30 d after adoptive transfer of OVA-specific Th1 or Th2 cells (107 cells per mouse) into naive BALB/c mice intravenously, animals were daily exposed intranasally to PBS, 1 μg OVA alone, or OVA plus 0.5 μg IL-18 in 50 μl PBS for 3 d. For the blockade of IL-13 in vivo, 20 μg sIL-13Rα2-Fc or 20 μg control human IgG were daily administered intranasally as the mixed form with OVA and IL-18 for 3 d. 24 h after the final exposure to antigen, AHR in response to increasing concentrations of inhaled β-Mch (A) and inflammatory cell composition of BALF (B) were examined as described in Fig. 2. Representative results of four animals are shown.
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fig5: Effect of the IL-13 blockage on IL-18 induced AHR and eosinophilia in mice receiving memory Th1 cells. 30 d after adoptive transfer of OVA-specific Th1 or Th2 cells (107 cells per mouse) into naive BALB/c mice intravenously, animals were daily exposed intranasally to PBS, 1 μg OVA alone, or OVA plus 0.5 μg IL-18 in 50 μl PBS for 3 d. For the blockade of IL-13 in vivo, 20 μg sIL-13Rα2-Fc or 20 μg control human IgG were daily administered intranasally as the mixed form with OVA and IL-18 for 3 d. 24 h after the final exposure to antigen, AHR in response to increasing concentrations of inhaled β-Mch (A) and inflammatory cell composition of BALF (B) were examined as described in Fig. 2. Representative results of four animals are shown.

Mentions: As IL-13 is reported to participate in airway inflammation and AHR (16–19), we next blocked the function of this cytokine by administration of IL-13 antagonist into the mice receiving Th1 cells (Fig. 5). We administered a soluble IL-13Rα2–human Fc fusion protein (IL-13R-Fc), which selectively binds to and neutralizes IL-13 but not IL-4 (34, 54), to these mice and compared them to mice that received control protein. Although this treatment significantly diminished the number of eosinophils in BALF (Fig. 5 B), little effect was seen in AHR upon Mch challenge (Fig. 5 A). In contrast, as previously reported, administration of IL-13 antagonist diminished both AHR and the number of eosinophils in BALF from Th2-transferred and OVA-stimulated mice (Fig. 5 B). Therefore, we could exclude the possibility that IL-13 is responsible for inducing AHR in mice receiving Th1 cells. Because the number of eosinophils was markedly diminished by neutralization of IL-13, these inflammatory cells were not involved in AHR in this experimental asthma model.


Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse.

Sugimoto T, Ishikawa Y, Yoshimoto T, Hayashi N, Fujimoto J, Nakanishi K - J. Exp. Med. (2004)

Effect of the IL-13 blockage on IL-18 induced AHR and eosinophilia in mice receiving memory Th1 cells. 30 d after adoptive transfer of OVA-specific Th1 or Th2 cells (107 cells per mouse) into naive BALB/c mice intravenously, animals were daily exposed intranasally to PBS, 1 μg OVA alone, or OVA plus 0.5 μg IL-18 in 50 μl PBS for 3 d. For the blockade of IL-13 in vivo, 20 μg sIL-13Rα2-Fc or 20 μg control human IgG were daily administered intranasally as the mixed form with OVA and IL-18 for 3 d. 24 h after the final exposure to antigen, AHR in response to increasing concentrations of inhaled β-Mch (A) and inflammatory cell composition of BALF (B) were examined as described in Fig. 2. Representative results of four animals are shown.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2211833&req=5

fig5: Effect of the IL-13 blockage on IL-18 induced AHR and eosinophilia in mice receiving memory Th1 cells. 30 d after adoptive transfer of OVA-specific Th1 or Th2 cells (107 cells per mouse) into naive BALB/c mice intravenously, animals were daily exposed intranasally to PBS, 1 μg OVA alone, or OVA plus 0.5 μg IL-18 in 50 μl PBS for 3 d. For the blockade of IL-13 in vivo, 20 μg sIL-13Rα2-Fc or 20 μg control human IgG were daily administered intranasally as the mixed form with OVA and IL-18 for 3 d. 24 h after the final exposure to antigen, AHR in response to increasing concentrations of inhaled β-Mch (A) and inflammatory cell composition of BALF (B) were examined as described in Fig. 2. Representative results of four animals are shown.
Mentions: As IL-13 is reported to participate in airway inflammation and AHR (16–19), we next blocked the function of this cytokine by administration of IL-13 antagonist into the mice receiving Th1 cells (Fig. 5). We administered a soluble IL-13Rα2–human Fc fusion protein (IL-13R-Fc), which selectively binds to and neutralizes IL-13 but not IL-4 (34, 54), to these mice and compared them to mice that received control protein. Although this treatment significantly diminished the number of eosinophils in BALF (Fig. 5 B), little effect was seen in AHR upon Mch challenge (Fig. 5 A). In contrast, as previously reported, administration of IL-13 antagonist diminished both AHR and the number of eosinophils in BALF from Th2-transferred and OVA-stimulated mice (Fig. 5 B). Therefore, we could exclude the possibility that IL-13 is responsible for inducing AHR in mice receiving Th1 cells. Because the number of eosinophils was markedly diminished by neutralization of IL-13, these inflammatory cells were not involved in AHR in this experimental asthma model.

Bottom Line: Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18.Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro.Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, 663-8501, Japan.

ABSTRACT
Interleukin (IL)-18 was originally regarded to induce T helper cell (Th)1-related cytokines. In general, factors favoring interferon (IFN)-gamma production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid a background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their role in induction of bronchial asthma. Administration of antigen (Ag) induced both airway inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, the same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were coadministered with IL-18. Furthermore, mice having received IFN-gamma-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR after intranasal administration of Ag and IL-18. Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

Show MeSH
Related in: MedlinePlus