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

Abstract

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. 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. 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. Results: ovalbumin challenge induced strong immune and inflammatory responses with > 6-fold IGE level increases; 10- to 25-fold BaL eosinophil, neutrophil, and lymphocyte count increases; and > 1.5-fold IL-4 and IL-5 level increases (p < 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 < 0.05). individual treatments reduced oVa-mediated bronchiolar infiltration by 50% (p <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 < 0.05). 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.