Asia Pac Allergy.  2012 Oct;2(4):256-263. 10.5415/apallergy.2012.2.4.256.

Interferon-alpha inhibits airway eosinophila and hyperresponsiveness in an animal asthma model

• Kikkawa Y
• Sugiyama K
• Obara K
• Hirata H
• Fukushima
• Toda M
• Fukuda T

• KMID: 2397442
• DOI: http://doi.org/10.5415/apallergy.2012.2.4.256

Abstract

BACKGROUND
Asthma is characterized by a chronic inflammatory process involving high numbers of inflammatory cells and mediators which have multiple inflammatory effects on the airway. Interferon (IFN)-alpha, which is used widely for treating chronic hepatitis C, is reported to have an effect on patients with Churg-Strauss syndrome. Therefore, it may also be suitable for patients with severe asthma.
OBJECTIVE
We studied the effect of IFN-alpha on airway eosinophilia in a guinea pig model of asthma and the expression of adhesion molecules on human eosinophils and vascular endothelial cells.
METHODS
After antigen challenge, airway hyperresponsiveness and airway eosinophilia were measured in a guinea pig asthma model with or without airway IFN-alpha administration. Expression of adhesion molecules on eosinophils and cultured human umbilical vein endothelial cells (HUVECs) was also evaluated with or without IFN-alpha.
RESULTS
IFN-alpha inhibited eosinophil recruitment into the tracheal wall and improved airway hyperresponsiveness in sensitized guinea pigs. IFN-alpha also significantly suppressed IL-1 beta-induced intercellular adhesion molecule-1 (ICAM-1) expression on HUVECs. However, IFN-alpha did not suppress platelet-activating factor-induced macrophage antigen-1 expression on human eosinophils. IFN-alpha significantly inhibited eosinophil adhesion to IL-1 beta-induced HUVECs and migration through IL-1 beta induced HUVECs.
CONCLUSION
The findings suggest that the modulation of ICAM-1 in lung with pre-existing inflammation following treatment with IFN-alpha may be a novel and selective treatment for control of chronic airway inflammation and hyperresponsiveness associated with asthma.

Keyword

Adhesion molecule; Asthma; Eosinophil; Interferon-alpha; Intercellular adhesion molecule-1; Macrophage antigen-1

MeSH Terms

Animals*
Asthma*
Churg-Strauss Syndrome
Endothelial Cells
Eosinophilia
Eosinophils
Guinea Pigs
Hepatitis C, Chronic
Human Umbilical Vein Endothelial Cells
Humans
Inflammation
Intercellular Adhesion Molecule-1
Interferon-alpha*
Interferons
Interleukin-1
Interleukin-1beta
Lung
Macrophages
Intercellular Adhesion Molecule-1
Interferon-alpha
Interferons
Interleukin-1
Interleukin-1beta

Figure

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  Fig. 1 Sensitization and challenge protocols.

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  Fig. 2 Effect of IFN-alpha on eosinophil infiltration into tracheal wall of guinea pig. OVA-sensitized guinea pigs were intraperitoneally injected with IFN-alpha or saline 3 h before OVA challenge. Trachea were removed 24 h after antigen challenge and fixed in 10% formalin and embedded in paraffin, and 3-µm-thick sections were stained with May-Giemsa and Hansel solution. Eosinophils which had infiltrated into the trachea were counted. Eosinophil infiltration was inhibited dose dependently by IFN-alpha. Mean ± SEM values of 15 animals are presented.

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  Fig. 3 Effect of IFN-alpha on airway hyperresponsiveness in guinea pigs. OVA-sensitized guinea pigs were intraperitoneally injected with IFN-alpha or saline 3 h before antigen challenge. The airway hyperresponsiveness was examined 24 h after antigen challenge. Data are presented as a logarithm of PC200-Rrs-histamine. Airway hyperresponsiveness was inhibited dose dependently by IFN-alpha. Mean ± SEM values of 7 animals are presented. Rrs, respiratory resistance.

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  Fig. 4 Effect of IFN-alpha on IL-1 beta-induced ICMA-1 (A) and VCAM-1 (B) expression on HUVECs. HUVECs were pretreated with IFN-alpha for 30 min and stimulated with IL-1 beta for 4 h. Cells were stained with anti-ICAM-1 or anti-VCAM-1, and mean specific fluorescence was determined by flow cytometry. ICAM-1 expression was inhibi ted dose dependently by IFN-alpha, while VCAM-1 expression was inhibited by high-dose of IFN-alpha only. Mean ± SEM values of 8 samples are presented.

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  Fig. 5 Effect of IFN-alpha on human eosinophil adhesion to HUVECs. HUVECs were grown to confluence in 24-well plates. HUVEC monolayers were pretreated with IFN-alpha for 30 min before IL-1 beta for 4 h. Then, purified eosinophil suspensions were added to each well. After 1 h incubation at room temperature, supernatants were collected and counted as non-adherent cells. Data show adherent cells (%), which were calculated based on the number of eosinophils in the supernatants. Adherent eosinophils were inhibited dose dependently by IFN-alpha. Mean ± SE values of 6 samples are presented.

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  Fig. 6 Effect of IFN-alpha on human eosinophil transmigration through HUVECs. HUVECs were pretreated with IFN-alpha and activated with IL-1 beta. Purified human eosinophils were added to upper wells. After 2 h incubation at 37℃ in a humidified CO2 (5%) incubator, lower well supernatants were collected and counted as transmigrated wells. Data are shown as migrated cells (%), which were calculated based on the number of eosinophils in the lower chamber. High-dose IFN-alpha significantly inhibited migration of eosinophils. Mean ± SE values of 10 samples are presented.

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