Dual CCR1+3 Monoclonal Antibody Therapy Alleviates Allergic Rhinitis-Asthma Syndrome in Mice via Suppressing Th2 Inflammation

Combined Allergic Rhinitis and Asthma Syndrome (CARAS) is characterized by Th2-driven inflammation, eosinophil infiltration, and chemokine-mediated immune responses. While CCR3 monoclonal antibody (CCR3mAb) exhibits therapeutic potential in allergic rhinitis, the roles of CCR1 monoclonal antibody (CCR1mAb) and its combination with CCR3mAb in CARAS remain unclear. Objective: This study aimed to evaluate the efficacy of CCR1mAb, CCR3mAb, and their combination in alleviating CARAS symptoms and elucidate the underlying mechanisms. Methods: Ovalbumin-sensitized and challenged CARAS mice were divided into six groups: normal control (NC), CARAS model, CCR1mAb (10 mg/kg), CCR3mAb (10 mg/kg), CCR1 + 3mAb combination (10 mg/kg each), and dexamethasone (DXMS, 5 mg/kg). Assessments included behavioral observations (sneezing/rubbing frequency), histopathology (HE/Masson staining), ELISA (Th2 cytokines), qPCR (CCR1 + 3 mRNA), and immunohistochemistry. Results: Both monotherapy and combination therapy significantly alleviated nasal symptoms (sneezing: P < 0.05; rubbing: P < 0.01 vs. CARAS) and reduced eosinophil infiltration (CARAS: 39.33 ± 2.52 vs. combination: 24.33 ± 5.69, P < 0.001). Histopathological improvements included reduced mucosal thickness (CARAS: 242.6 ± 33.33 µm vs. combination: 161.9 ± 16.91 µm, P < 0.01) and collagen deposition. Mechanistically, CCR1 + 3mAb synergistically suppressed Th2 cytokines (IL-4: 277.8 ± 20.27 pg/mL vs. CARAS: 464.8 ± 57.99, P < 0.001) and downregulated CCR1 + 3 mRNA expression (P < 0.01 vs. CARAS). However, no significant difference was observed between monotherapy and combination groups (P > 0.05), suggesting limited synergistic effects. Conclusion: CCR1mAb and CCR3mAb, alone or combined, ameliorated CARAS by targeting Th2 inflammation and airway remodeling. Although the combination did not exhibit marked synergy (potentially due to suboptimal dosing or compensatory pathways), it highlights the therapeutic potential of dual CCR1 + 3 targeting.