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Randomized Controlled Trial
. 2016:2016:4173962.
doi: 10.1155/2016/4173962. Epub 2016 Apr 3.

Effects of Low-Dose and Long-Term Treatment with Erythromycin on Interleukin-17 and Interleukin-23 in Peripheral Blood and Induced Sputum in Patients with Stable Chronic Obstructive Pulmonary Disease

Caimei Tan  1 , Huijuan Huang  1 , Jianquan Zhang  1 , Zhiyi He  1 , Xiaoning Zhong  1 , Jing Bai  1
Affiliations
Randomized Controlled Trial

Effects of Low-Dose and Long-Term Treatment with Erythromycin on Interleukin-17 and Interleukin-23 in Peripheral Blood and Induced Sputum in Patients with Stable Chronic Obstructive Pulmonary Disease

Caimei Tan et al. Mediators Inflamm. 2016.

Abstract

Objective: To study the effects of low-dose and long-term treatment with erythromycin on IL-17 and IL-23, in peripheral blood and induced sputum, in patients with stable chronic obstructive pulmonary disease (COPD).

Methods: Patients were randomly divided into placebo-treated group, group A (12 months of additive treatment with erythromycin, N = 18), and group B (6 months of additive treatment with erythromycin followed by 6 months of follow-up, N = 18). Inflammatory cells in induced sputum, pulmonary function, and the 6-minute walk distance (6MWD) were analyzed. Concentrations of IL-17 and IL-23 in peripheral blood and sputum were measured using enzyme-linked immunosorbent assays.

Results: After treatment, sputum and peripheral blood concentrations of IL-17 and IL-23 significantly decreased in groups A and B compared with placebo-treated group. There were no significant differences after erythromycin withdrawal at months 9 and 12 in group B compared with placebo-treated group. An increase in 6MWD was observed after treatment.

Conclusions: Erythromycin was beneficial and reduced airway inflammation in COPD patients. Underlying mechanisms may involve inhibition of IL-17 and IL-23 mediated airway inflammation. COPD patients treated with erythromycin for 6 months experienced improved exercise capacity. Finally, treatment for 12 months may be more effective than treatment for 6 months.

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Figures

Figure 1
Figure 1
(a) The effects of erythromycin on the number of inflammatory cells in induced sputum (106/mL) in chronic obstructive pulmonary disease patients at baseline and after 3, 6, 9, and 12 months of treatment. There was a significant reduction in total cell counts and neutrophil counts after erythromycin treatment from baseline to 3, 6, 9, and 12 months in group A (all P values < .01) and from baseline to 3 and 6 months in group B (all P values < .01). There was a significant decrease in total cell counts and neutrophil counts at all time points in group A (all P values < .05) and after 3 and 6 months in group B (all P values < .05) compared to the placebo-treated group. (b) The effects of erythromycin on the ratio of inflammatory cells in induced sputum (%) in chronic obstructive pulmonary disease patients at baseline and after 3, 6, 9, and 12 months of treatment. Significant reductions in the neutrophil ratio were observed after erythromycin treatment from baseline to 3, 6, 9, and 12 months in group A (all P values < .01) and to 3 and 6 months in group B (all P values < .01). Compared with placebo-treated group, the significant decreases were also observed in the neutrophil ratio after 3, 6, 9, and 12 months of treatment in group A (all P values < .05) and after 6 months in group B (P = .029). Increases in the macrophage ratio from baseline to 3, 6, 9, and 12 months in group A (all P values < .01) and 6 months in group B (P = .004) were observed and compared to placebo; similar increases were significant after 6, 9, and 12 months of treatment with erythromycin in group A (all P values < .05) and 6 months in group B (P = .040).
Figure 2
Figure 2
The effects of erythromycin treatment on the concentrations (pg/mL) of IL-17 and IL-23 in sputum from patients with chronic obstructive pulmonary disease at baseline and after 3, 6, 9, and 12 months of treatment. Erythromycin significantly decreased the levels of IL-17 in the sputum after 6, 9, and 12 months of treatment in group A (all P values < .001) and after 6 months in group B (P < .001) compared to the placebo-treated group. A similar change was observed in IL-23 in patient sputum after 6, 9, and 12 months (all P values < .001) in group A and after 6 months of treatment (P < .001) in group B compared to the placebo-treated group. Nine and 12 months after erythromycin was discontinued in group B, both IL-17 (P = .06 and P = .35, resp.) and IL-23 (P = .07 and P = .63, resp.) in sputum showed no differences compared to the placebo-treated group.
Figure 3
Figure 3
The effects of erythromycin treatment on the concentrations (pg/mL) of IL-17 and IL-23 in chronic obstructive pulmonary disease patients at baseline and after 3, 6, 9, and 12 months of treatment. Erythromycin significantly decreased the levels of IL-17 in serum after 3, 6, 9, and 12 months of treatment in group A (all P values < .001) and after 3 and 6 months in group B (all P values < .001) compared to the placebo-treated group. A similar change in IL-23 in serum was observed after 3, 6, 9, and 12 months of treatment in group A (all P values < .05) and after 3 and 6 months in group B (P = .003 and P < .001, resp.) compared to the placebo-treated group. After 9 and 12 months (after erythromycin was discontinued) in group B, both IL-17 (P > .99 and P = .90, resp.) and IL-23 (P = .67 and P > .99, resp.) in serum showed no differences compared to the placebo-treated group.
Figure 4
Figure 4
The effect of erythromycin on six-minute walk distance (6MWD, m) in chronic obstructive pulmonary disease patients at baseline and after 3, 6, 9, and 12 months of treatment. Erythromycin did significantly improve the 6MWD after 6, 9, and 12 months of treatment in group A (all P values < .05) and after 6 months of treatment in group B (P = .038) compared to the placebo-treated group.
Figure 5
Figure 5
(a) Correlation between inflammatory cytokines including IL-17 and IL-23 in both sputum and serum and sputum neutrophil ratios. (b) Correlation between inflammatory cytokines including IL-17 and IL-23 in both sputum and serum and sputum macrophage ratios.
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