Increased serum IL‑41 associated with acute exacerbation of chronic obstructive pulmonary disease

Abstract

Interleukin (IL)-41 is a novel immunomodulatory cytokine involved in the pathogenesis of several inflammatory and metabolic illnesses. However, it remains unclear how IL-41 contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, the aim of the present study was to explore the correlation between the expression level of IL-41 and acute exacerbation of COPD (AECOPD). In total, 107 patients with COPD and 56 healthy controls were recruited from the First Affiliated Hospital of Ningbo University (Ningbo, China). Serum IL-41, IL-6, and matrix metalloproteinase-2 (MMP-2) levels were evaluated using enzyme-linked immunosorbent assay. Serum amyloid A (SAA) and C-reactive protein (CRP) levels were assessed in the hospital laboratory. The levels of IL-41 were higher in the AECOPD group than in the stable COPD (SCOPD) and control groups (P<0.0001). IL-6, SAA and CRP levels, the percentage of neutrophils, as well as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were higher in the AECOPD group than those in the SCOPD and control groups. The smoking index was positively correlated with serum IL-41, CRP and SAA levels. The expression level of IL-41 was correlated with the number of acute exacerbations, severity of the exacerbations, and COPD assessment test scores in the AECOPD group. Examination of the receiver operating characteristic (ROC) curves showed that IL-41, especially when combined with other inflammatory factors, had a specific diagnostic value for AECOPD. According to the ROC curve analysis, the area under the curve (AUC) for IL-41 was 0.742 (P=0.051), and the AUC for IL-41 combined with other inflammatory factors was 0.925 (P=0.030). Increased serum IL-41 levels were associated with AECOPD and may play a role in the monitoring and evaluation of COPD.

Keywords: C-reactive protein; acute exacerbation; chronic obstructive pulmonary disease; interleukin-41; interleukin-6; serum amyloid A.

Figure 1

Inclusion and exclusion criteria for patients with COPD and HC. COPD, chronic obstructive pulmonary disease; HC, healthy controls; CRP, C-reactive protein; SAA, serum amyloid A; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; SCOPD, stable chronic obstructive pulmonary disease.

Figure 2

Concentrations of IL-41 in serum. ^****P<0.0001. IL-41, interleukin-41; SCOPD stable chronic obstructive pulmonary disease; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; ns, not significant.

Figure 3

Concentrations of serum cytokines. Concentrations of (A) IL-6, (B) MMP-2, (C) SAA and (D) CRP in serum. ^*P<0.05, ^***P<0.001 and ^****P<0.0001. IL-6, interleukin 6; MMP-2, matrix metalloproteinase-2; SAA, serum amyloid A; CRP, C-reactive protein; SCOPD, stable chronic obstructive pulmonary disease; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; ns, not significant.

Figure 4

Relationship between IL-41 and AECOPD. (A) Concentrations of IL-41 according to the number of acute exacerbations. (B) The concentrations of IL-41 according to degree of the exacerbation in hospitalized patients. (C) Concentrations of IL-41 according to mMRC. ^*P<0.05, ^**P<0.01 and ^****P<0.0001. IL-41, interleukin-41; mMRC, modified (British) Medical Research Council; ns, not significant.

Figure 5

Correlation of IL-41 with CAT and PLR. (A) Correlation of IL-41 with CAT. r=0.3337, P=0.0015. (B) Correlation of IL-41 with PLR. r=0.5602, P<0.001. IL-41, interleukin-41; CAT, chronic obstructive pulmonary disease assessment test; PLR, platelet to lymphocyte ratio.

Figure 6

Correlation of smoking index and serum cytokines. (A) Correlation of IL-41 with smoking index. r=0.3178, P=0.0245. (B) Correlation of CRP with smoking index. r=0.2568, P=0.0011. (C) Correlation of SAA with smoking index. r=0.4249, P<0.0001. (D) Correlation of IL-6 with smoking index. r=0.05883, P=0.4557. (E) Correlation of MMP-2 with smoking index. r=0.1289, P=0.1011. IL-41, interleukin-41; CRP, C-reactive protein; SAA, serum amyloid A; IL-6, interleukin 6; MMP-2, matrix metalloproteinase-2.

Figure 7

ROC curves. (A) ROC curves indicating the diagnostic value of IL-41, IL-6, SAA and CRP in AECOPD and SCOPD. (B) ROC curves indicating the diagnostic value of IL-41 combined with IL-6, MMP-2, SAA and CRP in AECOPD and SCOPD. ROC, receiver operating characteristic; IL-41, interleukin-41; IL-6, interleukin 6; MMP-2, matrix metalloproteinase-2; SAA, serum amyloid A; CRP, C-reactive protein; AECOPD, acute exacerbation of chronic obstructive pulmonary disease; SCOPD, stable chronic obstructive pulmonary disease.