Local IL-10 replacement therapy was effective for steroid-insensitive asthma in mice.

Abstract

Subgroups of patients with severe asthma showing marked increases in sputum eosinophils and/or neutrophils are insensitive to corticosteroids. Previous reports have shown that exogenous administration of an anti-inflammatory cytokine, interleukin (IL)-10 negatively regulated both eosinophilic and neutrophilic migration into tissues. The objective of this study was to elucidate whether intratracheal IL-10 administration suppresses asthmatic responses in a steroid-insensitive model of mice. Ovalbumin (OVA)-sensitized BALB/c mice were intratracheally challenged with OVA at 500 µg/animal four times. Dexamethasone (1 mg/kg, intraperitoneal) or IL-10 (25 ng/mouse, intratracheal) was administered during the multiple challenges. The number of leukocytes, expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL-10 receptor in the lung, and the development of airway remodeling and hyperresponsiveness were evaluated after the fourth challenge. Consistent with our previous study, dexamethasone hardly suppressed the development of airway remodeling and hyperresponsiveness. Although intratracheal IL-10 administration did not affect the development of airway remodeling, the infiltration of eosinophils and neutrophils, and the development of airway hyperresponsiveness were significantly inhibited. Moreover, IL-10 administration significantly decreased the numbers of ICAM-1+ and VCAM-1+ pulmonary vascular endothelial cells, which express IL-10 receptor 1, even though neither production of eosinophilic nor neutrophilic cytokines in the lung was inhibited. Therefore, IL-10 can suppress eosinophil and neutrophil infiltration by inhibiting the proliferation of ICAM-1+ and VCAM-1+ pulmonary vascular endothelial cells, resulting in inhibition of airway hyperresponsiveness in steroid-insensitive asthmatic mice. IL-10 replacement therapy may be clinically useful for the treatment of steroid-insensitive asthma.

• Authors: Masaya Matsuda, Miki Inaba, Junpei Hamaguchi, Hiro Tomita, Miyu Omori, Hayato Shimora, Harumi Sakae, Kazuyuki Kitatani, Takeshi Nabe
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 110 Pg. 109037 (Sep 2022) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 35810490 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Receptors, Interleukin-10
• Steroids
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• Interleukin-10
• Dexamethasone
• Ovalbumin

Topics

• Airway Remodeling
• Animals
• Asthma (drug therapy)
• Bronchoalveolar Lavage Fluid
• Cytokines (metabolism)
• Dexamethasone (pharmacology, therapeutic use)
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Eosinophils
• Intercellular Adhesion Molecule-1
• Interleukin-10 (pharmacology)
• Mice
• Mice, Inbred BALB C
• Ovalbumin
• Receptors, Interleukin-10
• Respiratory Hypersensitivity
• Steroids (pharmacology)
• Vascular Cell Adhesion Molecule-1 (metabolism)