Changes in serum hypoxia-inducible factor-1α and erythropoietin in allergic rhinitis patients: Correlation with the Th inflammatory profile and disease comorbidities

Abstract

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.