Objectives: The balance between proinflammatory IFN-γ Th1 vs. the anti-inflammatory allergy-mediating IL-4-heralded Th2 reactions is pivotal in IgE-mediated allergic rhinitis (AR). Hypoxia-Inducible Factor (HIF)-1α is inducible by hypoxia and various cytokines. HIF-1α activates different anti-pathogen and allergic immune cells. This cross-sectional study assessed the changes in serum HIF-1α and its dependent erythropoietin (EPO) levels among hospital-characterized AR patients. Type of the immune reaction, Th1 vs. Th2, was stratified based on the calculated IL-4/IFN-γ direct ratio, after being measured using specific ELISA assays.
Methods: 147 AR patients (83 males/64 females), and age-, BMI-, and gender-matched 24 healthy controls (13 males/11 females) were sequentially enrolled at ENT Unit, Prince Muteb General Hospital, Sakaka, Saudi Arabia. Measurement of serum parameters was carried out using specific ELISA assays.
Results: Contrary to the majority of previous publications, all controls and the majority of patients (n = 137/147) exhibited naive Th0 immune response. IFN-γ and HIF-1α levels were greater in controls than in patients (168.9 ± 173.9 vs 108 ± 94.5 pg/mL; p<.012) and controls had a lower IL-4/IFN-ratio (2.439 ± 0.897 vs 3.33 ± 1.19; p<.001) than patients. The HIF-1α results disagree with earlier studies. Due to the wide inter-individual variations, serum IL-4 and EPO levels in controls were non-significantly higher than patients. Lower IL-4 levels (267.3 ± 79.95 vs 353.4 ± 320.6 pg/mL; p < .01) and the ratio (2.814 ± 1.335 vs 3.431 ± 1.137; p < .05) were associated with obstructive sleep apnea. Lower ratio was also associated with inferior turbinate hypertrophy (3.051 ± 1.026 vs 3.787 ± 1.310; p < .001). EPO and IL-4 levels were lower in patients with deviated nasal septum (66.69 ± 26.81 vs 84.24 ± 61.5 pg/mL; p < .021; and 299.5 ± 137.3 vs 391.1 ± 52.780 pg/mL; p < .001, respectively). Significant correlations were found between the recorded levels and AR comorbidities.
Conclusion: These results confirmed a pathogenic implication for HIF-1α and IFN-γ in AR that warranted future bigger and longitudinal studies.
Keywords: IFN-γ; IL-4; IL-4/IFN-γ ratio; allergic rhinitis; erythropoietin; hypoxia-inducible factor-1α.