Comparative Study of IL-33 and IL-6 Levels in Different Respiratory Samples in Mild-to-Moderate Asthma and COPD

Figures & data

Figure 1. IL-6 and IL-33 protein expression in bronchial mucosa samples, examples of rating based on the intensity of immunostaining (control – no staining; 1+, weak; 2+, intermediate; and 3+, strong).

Table 1. Clinical characteristics of patients with asthma and COPD.

	Asthma (n = 22)	COPD (n = 33)	p
Male/Female (n)	11/11	15/18	0.788
Age (years)	51(32–60)	67(59–72)	<0.005
BMI (kg/m^2)	27.4(25.9–31.2)	26.2(22.9–30)	0.137
Atopic/non-atopic	14/8	8/25
Never smokers/ex-smokers/current smokers, n (%)	19/3/0 (86/14/0)	0/19/14 (0/58/42)	<0.001
Smoking history (pack-years)	0 (0–0)	45 (35–60)	<0.001
Duration of symptoms (months)	56.5 (30–120)	60 (24–120)	0.888
Pre-bronchodilator FEV1% of predicted	88.5 (72–99)	67 (54–75)	<0.001
Pre-bronchodilator FEV1/FVC (%)	63.5 (62–71)	50 (46–56)	<0.001
Post-bronchodilator FEV1% of predicted	99 (85–103)	71 (65–80)	<0.001
Post-bronchodilator FEV1/FVC (%)	69 (64–75)	52 (48–56)	<0.001
RV % of predicted	128.5 (116–141)	173 (141–187)	<0.001
TLC % of predicted	115 (107–126)	125 (114–131)	0.042

Results are presented as median and IQR. Analyses were made using Fisher's exact test, Mann-Whitney U test. The bolded values are statistically significant (p < 0.05) COPD – chronic obstructive pulmonary disease; BMI – body mass index; FEV₁ – forced expiratory volume at first second; FVC-forced vital capacity; TLC- total lung capacity; RV – residual volume.

Table 2. Cytokine expression and cells count in different biological samples from patients with asthma and COPD.

	Asthma (n = 22)	COPD (n = 33)	p
Eosinophil count
Blood eosinophils x10^9/l	0.22 (0.17–0.42)	0.16 (0.1–0.22)	0.027
Sputum eosinophils (% of nonsquamous cells)	10 (2–28)	2 (0–5)	0.005
Eosinophil count in biopsy (n/mm^2)	9.5 (5.3–15.8)	1 (0–2.1)	<0.001
Neutrophil count
Blood granulocytes x10^9/l	3.6 (2.5–4.4)	3.8 (3.1–4.8)	0.23
Sputum neutrophils (% of nonsquamous cells)	38 (25–55)	73 (57–87)	<0.001
mRNA cytokine expressions in induced sputum cells
IL-6 mRNA expression (fold change)	1.8 (0.6–11.9)	0.77 (0.09–10.7)	0.379
IL-33 mRNA expression (fold change)	0.12 (0.004–1.7)	0.62 (0.06–2.1)	0.764
Bronchial mucosa biopsy
Tissue expression of IL-6	1 (1–2)^*	3 (2–3)	<0.001
Tissue expression of IL-33	3 (2–3)^*	3 (2–3)	0.601
lymphocytes CD4+ (n/mm^2)	16 (14–22)^*	17 (9–22)	0.594
lymphocytes CD8+ (n/mm^2)	18 (12–24)^*	13 (10–19)	0.123
CD4/CD8 ratio	0.93 (0.6–1.3)^*	1.1 (0.7–1.4)	0.690

Results are presented as median and IQR. Analyses were made using Mann-Whitney U test. The bolded values are statistically significant (p < 0.05).

^* Concerned 21 asthma patients.

Figure 2. Concentrations of IL-6 and IL-33 in serum, induced sputum (IS), and exhaled breath condensate (EBC) from patients with asthma and chronic obstructive pulmonary disease (COPD).

Table 3. Spearman correlation coefficients for relationships between the levels/expression of IL-6 and IL-33 in the investigated materials from patients with asthma.

	Serum IL-6	Serum IL-33	IS IL-6	IS IL-33	IL-6 EBC	IL-33 EBC	IL-6 tissue expression	IL-33 tissue expression
IL-6 serum	1.0	−0.23	0.15	0.16	−0.01	−0.04	0.12	0.008
IL-6 IS	0.15	−0.16	1.0	0.46^*	−0.03	0.06	0.008	−0.24
IL-6 EBC	−0.01	0.17	−0.03	−0.001	1.0	−0.41	0.11	−0.32
IL-6 tissue expression	0.12	0.04	0.01	−0.05	0.11	0.29	1.0	0.49^*
IL-33 serum	−0.23	1.0	−0.16	0.17	0.17	0.18	0.04	−0.19
IL-33 IS	0.16	0.17	0.46^*	1.0	−0.001	0.19	−0.05	−0.28
IL-33 EBC	−0.04	0.18	0.06	0.20	−0.41	1.0	0.29	0.26
IL-33 tissue expression	0.01	−0.19	−0.24	−0.28	−0.32	0.26	0.49^*	1.0
Blood eosinophils %	0.05	−0.14	0.35	0.22	−0.45^*	0.3	−0.36	0.04
IS eosinophils %	0.04	0.22	0.22	0.31	−0.44^*	0.48^*	−0.03	0.27
Blood neutrophils %	−0.08	0.33	−0.54^*	−0.19	0.27	−0.43^*	−0.008	−0.14
IS neutrophils %	0.18	0.06	−0.38	−0.29	−0.01	−0.38	−0.09	−0.04

^* p < 0.05. The bolded values are statistically significant (p < 0.05).

IS – induced sputum; EBC – exhaled breath condensate.

Table 4. Spearman correlation coefficients for relationships between the levels/expression of IL-6 and IL-33 in the investigated materials from patients with chronic obstructive pulmonary disease (COPD).

	Serum IL-6	Serum IL-33	IS IL-6	IS IL-33	IL-6 EBC	IL-33 EBC	IL-6 tissue expression	IL-33 tissue expression
IL-6 serum	1.0	−0.21	−0.06	0.14	−0.005	−0.24	−0.42^*	0.05
IL-6 IS	−0.06	−0.04	1.0	0.15	−0.06	0.14	−0.22	−0.3
IL-6 EBC	−0.005	−0.08	−0.06	0.18	1.0	−0.6^*	−0.15	−0.09
IL-6 tissue expression	−0.42^*	0.19	−0.22	0.09	−0.15	0.12	1.0	0.16
IL-33 serum	−0.21	1.0	−0.05	0.02	−0.09	0.15	0.19	0.12
IL-33 IS	0.14	0.02	0.15	1.0	0.18	0.06	0.09	−0.2
IL-33 EBC	−0.24	0.12	0.14	0.06	−0.6^*	1.0	0.12	−0.1
IL-33 tissue expression	0.05	0.12	−0.3	−0.2	−0.09	−0.1	0.16	1.0
Blood eosinophils %	−0.06	0.07	−0.06	−0.09	−0.02	−0.03	−0.01	−0.26
IS eosinophils %	−0.48^*	−0.04	0.22	−0.1	−0.05	0.08	0.04	−0.21
Blood neutrophils %	0.16	−0.33	0.01	0.12	0.08	−0.13	−0.28	−0.03
IS neutrophils %	0.23	−0.18	−0.04	0.28	0.34	−0.22	0.07	−0.04

^* p < 0.05. The bolded values are statistically significant (p < 0.05).

IS – induced sputum; EBC – exhaled breath condensate.

Figure 3. Distribution of tissue IL-6 and IL-33 protein expression in bronchial mucosa biopsy samples in patients with asthma (n = 21) and chronic obstructive pulmonary disease (n = 33). The X-axis presents the intensity of the immunostainings (■ 0, ■1+,■ 2+,■ 3+) separately for asthma and COPD groups.