IL-1α antibody inhibits dose-dependent exacerbation of eosinophilic inflammation by crude house-dust-mite antigen in the conjunctiva of an atopic keratoconjunctivitis mouse model

• Published in: Current eye research Vol. 46; no. 8; pp. 1115 - 1124
• Main Authors: Shiraki, Yukiko, Shoji, Jun, Inada, Noriko, Tomioka, Akiko, Yamagami, Satoru
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.08.2021
• Subjects: Animals; Antibodies - therapeutic use; Antigens - adverse effects; Atopic keratoconjunctivitis; Chemokines - genetics; Chemokines - metabolism; Conjunctiva - immunology; Conjunctivitis, Allergic - chemically induced; Conjunctivitis, Allergic - genetics; Conjunctivitis, Allergic - immunology; Conjunctivitis, Allergic - therapy; Dermatophagoides farinae - immunology; Disease Models, Animal; Dose-Response Relationship, Drug; eosinophil; Eosinophils - immunology; Female; Fluorescent Antibody Technique, Indirect; house-dust-mite; IL-13; Inflammation - chemically induced; Inflammation - genetics; Inflammation - immunology; Inflammation - therapy; Interleukin-1alpha - immunology; Mice; mouse model; Real-Time Polymerase Chain Reaction; RNA, Messenger - genetics; Specific Pathogen-Free Organisms; house-dust-mite; Atopic keratoconjunctivitis; IL-13; mouse model; eosinophil
• DOI: 10.1080/02713683.2021.1874022
• ISSN: 0271-3683

To investigate whether crude house-dust-mite antigen exacerbates eosinophilic inflammation in the conjunctival tissues of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. An atopic keratoconjunctivitis mouse model was established by percutaneous sensitization and crude house-dust-mite antigen application in NC/Nga mice. To assess the dose-dependent response, conjunctival specimens from groups that were administered high- (High-HDM) or low-dose house-dust-mite antigen (Low-HDM) following percutaneous sensitization and the control without house-dust-mite antigen administration (control group) were evaluated. Histological examination and immunofluorescence staining were performed to determine eosinophil density and the number of IL-13-positive cells. Polymerase chain reaction array was used to obtain adaptive and innate immunity-related factor profile, and quantitative polymerase chain reaction was used to determine Il13, Il17a, Ccl11, and Ccl24 expression. Atopic keratoconjunctivitis model mice injected with anti-IL-1α antibody (IL-1α group) or vehicle (vehicle group) to the upper and lower eyelids before atopic keratoconjunctivitis development were evaluated. Eosinophil density in the conjunctiva increased with house-dust-mite antigen application in a dose-dependent manner. CD4, CXCL10, CCR6, C3, and IL-13 mRNA levels increased more than 5-fold in the conjunctiva of the High-HDM group animals compared to those in control animals. mRNA expression of Il13 and Ccl11 in the conjunctiva of the High-HDM group animals significantly increased compared with that in the Low-HDM and control group animals. Conversely, the eosinophil density and Il13 mRNA expression significantly decreased in the IL-1α group compared with those in the vehicle group. The house-dust-mite antigen increased eosinophilic infiltration and Il13 mRNA expression in the conjunctiva of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. These inflammatory alterations were partially alleviated by eyelid injection of anti-IL-1α antibody. These findings indicate that IL-1α-induced IL-13 production constitutes a major exacerbating factor for house-dust-mite antigen-induced atopic keratoconjunctivitis.