Additive anti-allergic effects of anti-interleukin-33 and anti-Siglec-F treatments in a murine model of allergic asthma

作者：Jang Tae Young; Park Chang Shin; Jeon Myung Shin; Heo Min Jeong; Na Kwangmin; Kim Young Hyo^*

来源：Central European Journal of Immunology, 2014, 39(4): 426-433.

DOI：10.5114/ceji.2014.47724

• cytokines
• asthma
• allergy
• interleukin-33
• Siglec-F

Background: Anti-interleukin-33 (anti-IL-33) and anti-Siglec-F antibodies have potent anti-allergic effects on murine allergic asthma and rhinitis and induce eosinophil apoptosis. %26lt;br%26gt;Objective: We aimed to determine whether post-sensitization with anti-IL-33/anti-Siglec-F treatments exhibited more potent effects compared to individual treatments in a murine allergic asthma model. %26lt;br%26gt;Material and methods: Twenty-five BALB/c mice were separated into five groups (n = 5): Group A(control), Group B (ovalbumin [OVA] challenge), Group C (OVA + anti-IL-33), Group D (OVA + anti-Siglec-F), and Group E (OVA + anti-IL-33 + anti-Siglec-F). Serum total/OVA-specific IgE, bronchoalveolar lavage (BAL) inflammatory cells and cytokines (IL-4 and IL-5), histopathological lung properties, and airway hyperreactivity were compared. %26lt;br%26gt;Results: Ovalbumin challenge induced strong immune and inflammatory responses with %26gt; 6-fold IgE level increases; 10- to 25-fold BAL eosinophil, neutrophil, and lymphocyte count increases; and %26gt; 1.5-fold IL-4 and IL-5 level increases (p %26lt; 0.05). Whereas anti-IL-33 reduced neutrophil counts, anti-Siglec-F and anti-IL-33/anti-Siglec-F reduced both eosinophil and neutrophil counts (p %26lt; 0.05). Individual treatments reduced OVA-mediated bronchiolar infiltration by 50% (p %26lt; 0.05). Ovalbumin challenge increased airway hyperreactivity by 4-fold (Group B; 2000.0 +/- 671.8% increase in Penh) compared to controls (Group A; 445.7 +/- 33.5% increase in Penh) (p = 0.016). The anti-IL-33 (Group C: 1579.4 +/- 973.6% increase in Penh) and anti-Siglec-F (Group D: 930.4 +/- 236.5%) groups demonstrated significantly reduced hyperreactivity (p = 0.029). Anti-IL-33/anti-Siglec-F therapy showed synergism towards neutrophil counts, IL-5 concentrations, bronchial infiltration, and hyperreactivity (p %26lt; 0.05). %26lt;br%26gt;Conclusions: Combination treatment with anti-IL-33/anti-Siglec-F had more potent anti-allergic effects, reducing eosinophilic infiltration through their additive effects in a murine allergic asthma model.