Impact of tobacco smoking on cytokine signaling via interleukin-17A in the peripheral airways

Figures & data

Table 1 Clinical characteristics for the cohort of long-term smokers (first cohort)

Clinical information	Nonsmokers	Long-term smokers without COPD	Long-term smokers with COPD
Subjects	20	19	17
Female/male	6/14	10/9	11/6
Age, years	54 (41–72)	54 (41–66)	62 (48–73)
FEV1 % pred	112 (75–139)	100 (81–131)	65 (45–105)
FEV1/FVC×100	80 (71–91)	77 (70–88)	56 (46–67)

Note: Data are represented as median (range).

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; pred, predicted.

Table 2 Clinical characteristics for the cohort of occasional smokers (second cohort)

Clinical information	Nonsmokers	Occasional smokers
Subjects	6	9
Female/male	3/3	6/3
Age, years	24 (22–36)	27 (22–44)
FEV1 % pred	112 (105–129)	109 (95–130)
FEV1/FVC×100	89 (74–99)	86 (75–99)

Note: Data are represented as median (range).

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Figure 1 Concentrations of IL-17A protein in cell-free BAL fluid samples from long-term smokers with (LTS + COPD, n=16) and without COPD (LTS, n=20), as well as from nonsmoking healthy controls subjects (NS, n=20).

Note: The data are shown as individual values, and the horizontal line indicates the median value for each group (nonparametric Kruskal–Wallis test with Dunn’s multiple comparison test: *P<0.05).
Abbreviations: BAL, bronchoalveolar lavage; COPD, chronic obstructive pulmonary disease; IL, interleukin; LTS, long-term smokers; NS, nonsmokers.

Figure 2 Levels of IL-17 in occasional smokers.

Notes: (A) Concentrations of IL-17A protein in cell-free BAL fluid samples in OS prior to and after short-term smoke exposure (OS + Expo). The data are shown as paired individual values and the horizontal line indicates the median value for each group (Wilcoxon signed rank test: NS = P>0.05; n=9). (B) Concentrations of IL-17A in BAL fluid in occasional smokers before exposure (n=11) and nonsmokers (nonparametric Mann–Whitney t-test: **P=0.0029, n=6).

Abbreviations: BAL, bronchoalveolar lavage; IL, interleukin; OS, occasional smokers; Expo, exposure; NS, nonsmokers.

Figure 3 Concentrations of IL-17A protein in cell-free BAL fluid samples in LTS versus OS prior to exposure.

Note: The data are shown as individual values and the horizontal line indicates the median value for each group (Mann–Whitney U test: *P<0.05; n=39 and 9).
Abbreviations: BAL, bronchoalveolar lavage; IL, interleukin; LTS, long-term smokers; OS, occasional smokers.

Figure 4 Immunohistochemical staining on biopsies from smokers.

Notes: (A) Correlation between IL-17A protein concentrations in cell-free BAL fluid samples and the number of CD8⁺ cells/mm² tissue in BBs from long-term, current smokers with COPD (Spearman rank correlation: r=0.7964; P=0.0006; n=15). (B) Immunohistochemistry images of BAL bronchial biopsies stained with (left) and without (right) CD8⁺ primary antibody. Scale bar respresents 191 μm. Immunohistochemistry images in 40× magnification of BAL.
Abbreviations: BAL, bronchoalveolar lavage; BB, bronchial biopsy; COPD, chronic obstructive pulmonary disease; IL, interleukin.

Figure 5 MMP-8 protein levels measured in BAL fluid.

Notes: Correlation between IL-17A and MMP-8 protein concentrations in cell-free BAL fluid samples from (A) subjects from all study groups, including long-term smokers with and without COPD as well as nonsmoking healthy control subjects (Spearman rank correlation: r=0.4069; P<0.005; n=56) and in (B) nonsmoking healthy control subjects only (Spearman rank correlation: r=0.8576; P<0.001; n=20).
Abbreviations: COPD, chronic obstructive pulmonary disease; IL, interleukin; MMP, matrix metalloproteinase.

Figure 6 Human beta defensin protein levels correlated to interleukin 17.

Notes: Correlation between IL-17A and HBD2 protein concentrations in cell-free BAL fluid samples from (A) subjects from all study groups, including long-term smokers with and without COPD as well as nonsmoking healthy control subjects (Spearman rank correlation; r=0.5172, P<0.0001; n=56); in (B) nonsmoking healthy control subjects only (Spearman rank correlation; r=0.4797, P<0.05; n=20); and (C) in long-term smokers with and without COPD (Spearman rank correlation; r=0.3608, P<0.05; n=36).
Abbreviations: COPD, chronic obstructive pulmonary disease; HBD2, human beta defensin 2; IL, interleukin.