Study population

The baseline characteristics of the 77 patients with AR included in our analysis are shown in Table 1. Overall, a higher proportion of patients included had no history of smoking and had been working indoors for a long time. Moreover, most of the patients in this study had a 1- to 5-year history of AR-related symptoms (nasal itching, sneezing, runny nose, and nasal congestion).

Table 1 Baseline characteristics of the patients with AR (n = 77) Concentration levels and correlation analysis of IL-36 family cytokines in the peripheral blood of patients with ARConcentration levels of IL-36 family cytokines in the peripheral blood of patients with AR

In the peripheral blood of patients with AR, the IL-36α concentration was highest, followed by IL-36Ra, IL-36γ, and IL-38, while IL-36β showed the lowest level (Fig. 1). Further comparisons between cytokines using the Kruskal-Wallis H test revealed that there were significant differences in concentration between cytokines (P < 0.01), except IL-36γ and IL-38.

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

Comparison of IL-36 family cytokine concentrations in the peripheral blood of patients with AR of different sexes and ages

Seventy-seven patients with AR were divided into a male group, a female group, a juvenile group (< 18 years) and an adult group (≥ 18 years) according to sex and age. The Mann-Whitney U test was used to analyze and compare the concentrations of IL-36 family cytokines in different groups. The results showed that the concentration level of IL-36α in the peripheral blood of juvenile patients was higher than that of adult patients, and the difference was statistically significant (P = 0.008), while there was no significant difference in the concentration of other cytokines of the IL-36 family between different sex and age groups (P > 0.05) (Table 2). We further used Point-biserial correlation and Spearman correlation to analyze the correlation between sex and age and IL-36 family cytokines, respectively. The results showed that neither sex nor age was significantly correlated with IL-36 family cytokines (P > 0.05). Therefore, sex and age were not considered confounding variables in this article.

Table 2 Concentrations of IL-36 family cytokines in the peripheral blood of patients with AR of different sexes and ages (pg/mL) Correlation analysis between IL-36 family cytokines in peripheral blood

Spearman rank correlation analysis was used to analyze the correlation between IL-36 family cytokines in peripheral blood, and the results showed that the IL-36α level in peripheral blood was positively correlated with IL-36γ level with a correlation coefficient of 0.28 (P = 0.013); the IL-36β level was positively correlated with IL-36Ra and IL-38 levels with correlation coefficients of 0.55 (P < 0.001) and 0.56 (P < 0.001), respectively; the IL-36γ level was positively correlated with IL-36Ra level with a correlation coefficient of 0.30 (P = 0.008); the IL-36Ra level was positively correlated with IL-38 level with a correlation coefficient of 0.45 (P < 0.001); and there was no correlation between other cytokine levels (P > 0.05) (Fig. 2).

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

SNOT-22 and VAS scores

Seventy-seven patients with AR underwent SNOT-22 scoring, and the median was 35 (IQR: 22, 49). VAS scores were calculated separately for nasal, ocular, and asthma-related symptoms in patients with AR. The total VAS score for nasal symptoms was defined as the sum of the VAS scores for the four symptoms of nasal itching, sneezing, runny nose and nasal congestion; the total VAS score for ocular symptoms was defined as the sum of the VAS scores for the four symptoms of ocular itching, lacrimation, eye redness and eye pain; the total VAS score for asthma-related symptoms was defined as the sum of the VAS scores for the four symptoms of cough, suffocation, wheezing, and squeezing sensation. The median total VAS score for nasal symptoms was 25 (IQR: 21, 29), the median VAS score for nasal itching symptom was 5 (IQR: 3, 8), the median VAS score for sneezing symptom was 8 (IQR: 5, 9), the median VAS score for runny nose symptom was 7 (IQR: 5, 9), and the median VAS score for nasal congestion symptom was 6 (IQR: 3, 8). The median total VAS score for ocular symptoms was 7 (IQR: 3, 12.50), the median VAS score for ocular itching symptom was 2 (IQR: 0.50, 5), the median VAS score for lacrimation symptom was 2 (IQR: 0, 4), the median VAS score for ocular redness symptom was 1 (IQR: 0, 3.50), and the median VAS score for eye pain symptom was 0 (IQR: 0, 2). The median total VAS score for asthma-related symptoms was 4 (IQR: 1, 10.50), the median VAS score for cough symptom was 1 (IQR: 0, 4), the median VAS score for suffocation symptom was 0 (IQR: 0, 3.50), the median VAS score for wheezing was 0 (IQR: 0, 2), and the median VAS score for squeezing was 0 (IQR: 0, 3).

Overall distribution of inhaled allergens

Of 77 patients with AR, 49 tested positive for allergen tIgE, yielding a positive rate of 63.64% (49/77). In the analysis of the number of positive inhaled allergens, 1 had the highest number of positive inhaled allergens and 4 or more had the lowest number (Table 3); the highest positive intensity of allergen sIgE had the highest number of grade 1 and the lowest number of grade 3 and 4 (Table 3). Analysis of inhaled allergen-positive types revealed that 53 enrolled patients were allergic to perennial inhalant allergens (house dust, Dermatophagoides pteronyssinus/Dermatophagoides farinae, cat dander/dog dander), 14 enrolled patients were allergic to seasonal inhalant allergens (cypress/elm/sycamore/willow/poplar, wormwood/ragweed, Penicillium punctatum/Cladosporium fumigatus/Aspergillus fumigatus/Alternaria alternata/Rhizopus/Mucor), and only 10 enrolled patients were allergic to both perennial allergens and seasonal allergens.

Table 3 Distribution of the number of positive inhaled allergens and the highest positive intensity of allergen sIgE in 77 patients with AR Analysis of the correlation between IL-36 family cytokine levels and subjective and objective assessment results of patients with ARAnalysis of the correlation between IL-36 family cytokine levels and VAS scores and SNOT-22 score

Spearman rank correlation analysis showed that there was no significant correlation between the concentration levels of IL-36 family cytokines in peripheral serum and SNOT-22 score, the total VAS score for nasal symptoms or the total VAS score for asthma-related symptoms in patients with AR (P > 0.05), while there was a positive correlation between the concentration level of IL-36α in peripheral serum and VAS score for nasal congestion symptom with a correlation coefficient of 0.26, and the difference was statistically significant (P = 0.023), indicating that the higher the concentration levels of IL-36α in peripheral blood of patients with AR, the more prominent their nasal congestion symptom. There was a positive correlation between the concentration level of IL-36β in peripheral serum and the total VAS score for ocular symptoms with a correlation coefficient of 0.27, and the difference was statistically significant (P = 0.020). Specifically, there was a positive correlation between the level of IL-36β in peripheral blood and VAS scores for ocular itching and eye pain symptoms with correlation coefficients of 0.25 and 0.24, respectively. The differences were statistically significant (P = 0.028, P = 0.034), indicating that the higher the levels of IL-36β in the peripheral blood of patients with AR, the more severe the symptoms of ocular itching and eye pain, and even the overall symptoms of the eyes; there was no correlation between the other members of IL-36 family cytokines and the VAS scores of patients’ symptoms (P > 0.05) (Table 4).

Table 4 Correlation analysis of IL-36 family cytokine concentration levels with VAS scores and SNOT-22 score in peripheral blood of 77 patients with AR Comparison of IL-36 family cytokine concentration levels in peripheral blood between patients with positive and negative inhaled allergen tIgE

The two independent samples t test or Mann-Whitney U test was used to compare the concentration differences of IL-36 family cytokines between the inhaled allergen tIgE-positive and tIgE-negative groups, and it was found that there were no significant differences in the concentration levels of IL-36α, IL-36β, IL-36γ, IL-36Ra, and IL-38 between the two groups (P > 0.05), indicating that tIgE positivity did not affect the concentrations of IL-36 family cytokines in the peripheral blood of patients with AR (Table 5).

Table 5 Comparison of IL-36 family cytokine concentration levels in peripheral blood between patients with positive and negative inhaled allergen tIgE (pg/mL) Correlation analysis of IL-36 family cytokine concentrations in peripheral blood with the number of positive inhaled allergens and the highest positive intensity of allergen sIgE

Spearman rank correlation analysis revealed that there was no correlation between IL-36 family cytokine levels in peripheral blood and the number of positive inhaled allergens or the highest positive intensity of allergen sIgE in patients with AR (P > 0.05) (Table 6).

Table 6 Correlation analysis of IL-36 family cytokine concentrations in peripheral blood with the number of positive inhaled allergens and the highest positive intensity of allergen sIgE Comparison of differences in IL-36 family cytokine concentrations in peripheral blood between the perennial allergen group, seasonal allergen group and mixed allergen group

According to inhalant allergen-positive types in patients with AR, 77 patients with AR were divided into 3 groups: allergic to perennial inhalant allergens only—perennial allergen group (53 cases), allergic to seasonal inhalant allergens only—seasonal allergen group (14 cases), and allergic to both perennial allergens and seasonal allergens—mixed allergen group (10 cases). By comparing the concentration levels of IL-36 family cytokines among the three groups, IL-36α, IL-36β, IL-36γ and IL-38 levels were found to be not significantly different among the three groups (P > 0.05). The concentration levels of IL-36Ra were significantly different among the three groups (P = 0.022), and further pairwise comparisons revealed that there was a difference in IL-36Ra levels between the perennial allergen group and the seasonal allergen group (P = 0.018), indicating that IL-36Ra levels in peripheral blood were higher in patients with AR with seasonal allergen allergy than in perennial allergen allergic patients (Table 7) (Fig. 3).

Table 7 Comparison of IL-36 family cytokine concentration differences in peripheral blood among the perennial allergen group, seasonal allergen group and mixed allergen group (pg/mL) 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