Correlations between IL-36 family cytokines in peripheral blood and subjective and objective assessment results in patients with allergic rhinitis

Abstract

Background: Interleukin (IL)-36 family cytokines have received increasing attention, especially in the fields of inflammation and immunity research. However, whether IL-36 family cytokine levels are correlated with the results of the assessment of allergic rhinitis (AR) and affect the severity of AR remains unknown. Therefore, this study aimed to investigate the correlations between IL-36 family cytokine levels and subjective and objective assessment results and to further analyze the possible mechanisms of IL-36 family cytokines in the development of AR.

Methods: An enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of the IL-36 family cytokines IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 in the peripheral blood of patients with AR. The condition of patients with AR was assessed by 22-item sino-nasal outcome test (SNOT-22) score, visual analogue scale (VAS) scores for disease severity, and serum inhalant allergen immunoglobulin E (IgE) detection. Correlations between IL-36 family cytokine levels and subjective and objective assessment results in patients with AR were analyzed.

Results: The concentration of IL-36α in the peripheral blood of patients with AR was the highest, and the concentration of IL-36β was the lowest. The concentration of IL-36α was higher in juvenile patients than in adult patients, and there was a difference in the IL-36Ra level between the perennial allergen group and the seasonal allergen group. There was a positive correlation between IL-36α level and IL-36γ level, IL-36γ level and IL-36Ra level, and IL-36Ra level and IL-38 level, and IL-36β level was positively correlated with IL-36Ra and IL-38 levels, respectively. IL-36α level was positively correlated with VAS score for nasal congestion symptom. IL-36β level was positively correlated with the total VAS score for ocular symptoms and VAS scores for ocular itching and eye pain symptoms. However, there was no correlation between the levels of all cytokines in IL-36 family and SNOT-22 score, the number of positive inhaled allergens, or the highest positive intensity of allergen specific immunoglobulin E (sIgE).

Conclusion: Peripheral blood IL-36 family cytokines play an important role in AR, and the concentrations of IL-36α and IL-36β were related to the severity of symptoms in patients with AR.

Keywords: Allergens; Allergic rhinitis; Interleukin-36; Symptom assessment.

Fig. 1

Concentrations of IL-36 family cytokines in the peripheral blood of 77 patients with AR. The data tested did not exhibit a normal distribution and were, therefore, described using the median and IQR. In patients with AR, the peripheral blood IL-36α concentration was highest, with a median of 6.71 × 10³ pg/mL (IQR: 5.12 × 10³, 9.46 × 10³); the IL-36β concentration was lowest, with a median of 87.86 pg/mL (IQR: 71.92, 99.41); the IL-36γ concentration was 332.79 pg/mL (IQR: 251.43, 387.65); the IL-36Ra concentration was 3.47 × 10³ pg/mL (IQR: 2.96 × 10³, 4.40 × 10³); and the IL-38 concentration was 316.18 pg/mL (IQR: 217.77, 455.62). IL interleukin; AR allergic rhinitis; IQR interquartile range

Fig. 2

Correlation analysis of IL-36 family cytokine concentration levels in the peripheral blood of 77 patients with AR. The tested data did not exhibit a normal distribution, so Spearman rank correlation analysis was used. The results showed that the IL-36α level was positively correlated with IL-36γ level (r = 0.28, P = 0.013), the IL-36β level was positively correlated with IL-36Ra and IL-38 levels (r = 0.55, P < 0.001; r = 0.56, P < 0.001), the IL-36γ level was positively correlated with IL-36Ra level (r = 0.30, P = 0.008), the IL-36Ra level was positively correlated with IL-38 level (r = 0.45, P < 0.001), and there was no correlation between the levels of the remaining cytokines (P > 0.05). IL interleukin; AR allergic rhinitis

Fig. 3

Patients with AR were divided into three groups according to different types of allergen positivity: perennial allergen group, seasonal allergen group and mixed allergen group. The test data did not conform to a normal distribution, so the Kruskal-Wallis H test was used to compare the differences in the levels of IL-36 family cytokines among the three groups, and the Bonferroni method was further used for pairwise comparison if the differences were statistically significant. (a) There was no significant difference in peripheral blood IL-36α concentration among the three groups of patients with AR; (b) There was no significant difference in peripheral blood IL-36β concentration among the three groups of patients with AR; (c) There was no significant difference in peripheral blood IL-36γ concentration among the three groups of patients with AR; (d) Peripheral blood IL-36Ra concentration in patients with AR in the seasonal allergen group was higher than that in the perennial allergen group with a statistically significant difference (P = 0.018), and there was no significant difference in peripheral blood IL-36Ra concentration between patients with AR in the mixed allergen group and those in the perennial allergen group and seasonal allergen group; (e) There was no significant difference in peripheral blood IL-38 concentration among the three groups of patients with AR. AR allergic rhinitis; IL interleukin