Blood MCP-1 levels are increased in chronic obstructive pulmonary disease patients with prevalent emphysema

Figures & data

Table 1 Clinical characteristics of COPD patients by phenotype and control subjects who provided blood samples

Subjects	Control nonsmokers	Control smokers	COPD-B	COPD-E
Subjects	18	9	23	22
M/F	8/10	4/5	19/4	20/2
Pack/years	–	38.5±24	51.21±29	40.44±31
Ex-smokers/current smokers	–	2/7	19/4	18/4
FEV1 (L)	3.34±1.2	3.2±0.8	1.19±0.52*,#	1.25±0.62*,#
FEV1%	116±6	102±8	55±24*,#	53±22*,#
FEV1/FVC (%)	79±4.1	74±11	46±14*,#	40±11*,#
RV (L)	1.95±0.2	2.3±0.6	3.20±1.02*,#	3.63±1.45*,#
RV%	95.8±3	91±2	119±41*,#	132±52*,#
VC (L)	–	–	2.56±0.68	3.01±1.0
VC%	–	–	77.7±19.5	82.4±18.1
DLCO (L)	–	–	3.75±1.72	3.89±2.91
DLCO%	–	–	50±21	40±16
6MWD (m)	–	–	343.32±127.9	428.20±120.8
Exacerbations/year	–	–	1.70±1.06	1.29±0.73

Notes: Data are presented as number or mean ± SD.

* p<0.05 compared with control smokers;

# p<0.05 compared with control nonsmokers (ANOVA). COPD-B, COPD patients with prevalent airway disease; COPD-E, COPD patients with prevalent emphysema.

Abbreviations: 6MWD, 6-minute walking test; ANOVA, analysis of variance; COPD, chronic obstructive pulmonary disease; DLCO, diffusing capacity of the lungs for carbon monoxide; F, female; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; M, male; RV, residual volume; VC, vital capacity.

Table 2 Quantification of molecules related to oxidative stress and cytokines in the blood

Molecules	Control non-smokers	Control smokers	COPD-B	COPD-E	Kruskal–Wallis
IL-1α (pg/mL)	0.2 (0–0.8)	0.9 (0–1.8)#	0 (0–1.3)*	0.3 (0–1.1)*	0.0402
IL-1β (pg/mL)	0 (0–2.5)	0 (0–5.2)	0.7 (0–2.7)	0.4 (0–2)	0.5877
IL-2 (pg/mL)	1.6 (0–7)	0 (0–7.4)	3.8 (0–9.6)	2.8 (0–7.7)	0.5242
IL-4 (pg/mL)	1.3 (0–2.2)	1.8 (0–6.6)	0 (0–4.5)	0 (0–2.9)	0.7530
IL-6 (pg/mL)	0.7 (0–4.6)	1.8 (0.9–19.2)#	2.4 (0.6–620.3)#	2.5 (0.9–27.9)#	<0.0001
IL-8 (pg/mL)	7.1 (3–148)	8.6 (4.9–1,017)	10.4 (3.9–1,207.8)#	15.9 (3.9–999.4)#	0.0273
IL-10 (pg/mL)	0 (0–1.9)	0 (0–1.7)	0 (0–2.6)	0 (0–2.2)	0.8823
TNF-α (pg/mL)	2.7 (1.2–22.4)	2.3 (1.8–14.8)	3.2 (1.4–56.6)	4.5 (1.6–14.4)	0.3500
IFN-γ (pg/mL)	0 (0–6.5)	3.4 (0–5.5)#	0.4 (0–18.3)	0.5 (0–6.7)	0.2711
EGF (pg/mL)	53.8 (3.5–197.2)	56.6 (11.1–163.0)	88.5 (8.5–203.8)#	103.6 (13.1–184)#	0.0253
MCP-1 (pg/mL)	182.1 (130.8–333.4)	234.4 (158–440.2)	245.9 (109.6–452.2)	292 (174.2–427.7)*,#	0.0187
VEGF (pg/mL)	132.3 (33.5–391.3)	165.6 (40.7–221.0)	143.0 (36.9–485.2)	179 (52.7–857.3)	0.3634
SOD1 (U/mL)	175 (132–207)	143 (138–1,333)	147 (36–284)#	150.50 (29–209)#	0.0388
GPx1 (U/L)	4,862 (4,141–6,847)	4,879 (3,136–7,216)	5,371 (2,230–8,364)	5,166 (2,091–11,193)	0.9249
F2-IsoPs (pg/mL)	26.8 (10–39.7)	70.7 (22.6–126.8)#	142.70 (72.2–476.3)*,#	111.95 (56.9–472.3)*,#	<0.0001

Notes: Data are presented as median and range. The Kruskal–Wallis test was used for multiple comparisons followed by the Mann–Whitney U test for comparison between groups:

* p<0.05, significantly different from control smokers;

# p<0.05, significantly different from control nonsmokers. The exact p-values are reported in Table 3 and in the “Results” section. Significant values are reported in bold. COPD-B, COPD patients with prevalent airway disease; COPD-E, COPD patients with prevalent emphysema.

Abbreviations: EGF, epidermal growth factor; F2-IsoPs, F2-isoprostanes; GPx, glutathione peroxidase; IFN, interferon; IL, interleukin; MCP, monocyte chemotactic protein; SOD, superoxide dismutase; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.

Table 3 Statistical analysis between groups regarding the oxidative stress molecules and cytokines reported in Table 2

Molecules	CNS vs CS; p-value	CNS vs COPD-B; p-value	CS vs COPD-B; p-value	CNS vs COPD-E; p-value	CS vs COPD-E; p-value	COPD-E vs COPD-B; p-value
IL-1α (pg/mL)	0.0064	0.9895	0.0119	0.3918	0.0408	0.4469
IL-1β (pg/mL)	0.5203	0.2026	0.7374	0.2479	0.7940	0.9367
IL-2 (pg/mL)	0.8977	0.1719	0.3902	0.4305	0.7441	0.4008
IL-4 (pg/mL)	0.7188	0.4863	0.6298	0.3624	0.4083	0.8116
IL-6 (pg/mL)	0.0064	<0.0001	0.3246	<0.0001	0.2963	0.7592
IL-8 (pg/mL)	0.1649	0.0292	0.8504	0.0047	0.3608	0.2469
IL-10 (pg/mL)	0.8774	0.7726	0.5715	0.6440	0.9306	0.4606
TNF-α (pg/mL)	0.9181	0.3056	0.4138	0.0843	0.2766	0.5780
IFN-γ (pg/mL)	0.0206	0.5457	0.1541	0.4465	0.3169	0.7420
EGF (pg/mL)	0.3284	0.0459	0.6298	0.0036	0.2400	0.1592
MCP-1 (pg/mL)	0.3545	0.1212	0.6599	0.0023	0.0453	0.1526
VEGF (pg/mL)	0.4105	0.5457	0.9833	0.0819	0.3841	0.2859
SOD1 (U/mL)	0.2216	0.0121	0.2758	0.0122	0.4083	0.7164
GPx1 (U/L)	0.5711	0.5909	0.9666	0.8406	0.6793	0.6911
F2-IsoPs (pg/mL)	0.0122	<0.0001	0.0081	,0.0001	0.0385	0.4652

Notes: CNS: n=18; CS: (n=9); COPD-B, COPD patients with prevalent airway disease; (n=23); COPD-E, COPD patients with prevalent emphysema (n=22). The p-values are obtained using the Mann–Whitney U test between groups for each of the molecules studied (reported in Table 2). Significant values are reported in bold.

Abbreviations: CNS, control nonsmoker; CS, control smoker; EGF, epidermal growth factor; F2-IsoPs, F2-isoprostanes; GPx, glutathione peroxidase; IFN, interferon; IL, interleukin; MCP, monocyte chemotactic protein; SOD, superoxide dismutase; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.

Figure 1 IL-6 is significantly increased in the blood of COPD patients with prevalent emphysema (E group), prevalent airway disease (B group), and CSs compared with CNSs (A); IL-8 is significantly increased in COPD-E and COPD-B compared with CNSs (B); EGF is significantly increased in COPD patients from COPD-E and COPD-B groups compared with CNSs (C); MCP-1 is significantly increased in COPD-E compared with CSs and CNSs (D); SOD-1 is significantly decreased in COPD-E and COPD-B compared with CNSs (E); F2-IsoPs is significantly increased in both COPD-B and COPD-E groups compared with CSs and CNSs, and CSs also showed higher levels compared with CNSs (F). Bar lines represent median values.

Note: COPD-B, COPD patients with prevalent airway disease; COPD-E, COPD patients with prevalent emphysema.
Abbreviations: CNS, control nonsmoker; COPD, chronic obstructive pulmonary disease; CS, control smoker; EGF, epidermal growth factor; F2-IsoPs, F2-isoprostanes; IL, interleukin; MCP, macrophage chemotactic protein; SOD, superoxide dismutase.

Figure 2 Regression analysis performed in all COPD patients (COPD-E and COPD-B groups) and CS and CNS groups showing correlations between F2-IsoPs and MCP-1 (A), IL-2 (B), IL-1β (C), IFN-γ (D), TNF-α (E), and SOD1 (F). All inflammatory molecules correlated positively and significantly with the oxidative stress marker F2-IsoPs. SOD1 correlated inversely and significantly with the oxidative stress marker F2-IsoPs.

Note: COPD-B, COPD patients with prevalent airway disease; COPD-E, COPD patients with prevalent emphysema.

Abbreviations: CNS, control nonsmoker; COPD, chronic obstructive pulmonary disease; CS, control smoker; F2-IsoPs, F2-isoprostanes; IFN, interferon; IL, interleukin; MCP, macrophage chemotactic protein; SOD, superoxide dismutase; TNF-α, tumor necrosis factor-α.

Figure 3 Regression analysis performed in all COPD patients (COPD-E and COPD-B groups) showing correlations between F2-IsoPs and IFN-γ (A), TNF-α (B), and IL-2 (C). All inflammatory molecules correlated positively and significantly with the oxidative stress marker F2-IsoPs.

Note: COPD-B, COPD patients with prevalent airway disease; COPD-E, COPD patients with prevalent emphysema.
Abbreviations: COPD, chronic obstructive pulmonary disease; F2-IsoPs, F2-isoprostanes; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor.