A potential inflammatory role of IL-31 in psoriatic arthritis: A correlation with Th17 cytokine profile

Abstract

The goals of our study were to determine the possible association of interleukin (IL)-31 with Th17 cytokine profile in serum and to quantify retinoic acid-related orphan receptor C (RORC) mRNA expression in psoriatic arthritis (PsA) patients. This cross-sectional study was conducted in 50 patients with PsA and 30 control subjects (CS) matched by age and gender. The cytokine serum levels were quantified by magnetic bead-based assay using the Bio-Plex MAGPIX system, and RORC mRNA expression was determined by quantitative polymerase chain reaction (qPCR). As a result, significant differences in IL-31 were observed between study groups (77.23 pg/mL in PsA vs 64.4 pg/mL in CS, P < 0.001) and Th17 cytokine profile serum levels (IL-17A: 6.36 pg/mL in PsA vs 2.97 pg/mL in CS, P = 0.02; IL-17F: 44.15 pg/mL in PsA vs 23.36 pg/mL in PsA, P = 0.01; IL-17E: 3.03 pg/mL in PsA vs 0.82 pg/mL in CS, P < 0.001; IL-21: 36.45 pg/mL in PsA vs 12.44 pg/mL in CS, P = 0.02); however, significant differences were not observed for IL-23 (31.2 pg/mL in PsA vs 53.26 pg/mL in CS, P = 0.58). Furthermore, positive correlations between IL-31 and Th17 cytokine profile serum levels were found (IL-17A: r_s = 0.64, P < 0.001; IL-17F: r_s = 0.73, P < 0.001; IL-17E: r_s = 0.70, P < 0.001; IL-21: r_s = 0.54, P = 0.002; IL-23: r_s = 0.5, P < 0.01). Regarding RORC gene expression, the PsA group showed an increase of 6.85-fold compared to the CS group. We did not find any association between the serum levels of cytokines and RORC gene expression. In conclusion, in PsA, there are increased serum levels of IL-31, IL-17A, IL-17F, IL-17E, and IL-21, but not IL-23. Moreover, there was a positive correlation of IL-31 with the Th17 cytokine profile and a high RORC gene expression. Altogether, these findings suggest a proinflammatory contribution of IL-31 in close association with the Th17 cytokine profile in PsA.

Keywords: IL-31; RORC; Th17 cytokine profile; mRNA expression; psoriatic arthritis.

Figure 1.

(a) RORC gene expression in PsA and CS. RORC gene expression stratified according to (b) Disease Activity Score-28 (DAS28), (c) pharmacological treatment, (d) evolution time of PsA, and (e) body mass index (BMI; kg/m²) in PsA patients. Analysis of relative expression was performed by the Pfaffl method. MTX: methotrexate.

Figure 2.

Quantification of IL-31 and Th17 cytokine profile in PsA and CS. Comparison of serum levels of (a) IL-17A, (b) IL-17F, (c) IL-17E, (d) IL-21, (e) IL-23 and (f) IL-31 between PsA and SC. Horizontal lines indicate median and 25th–75th percentiles of the cytokine serum levels. Statistical analysis was performed using Mann–Whitney U test. PsA= Psoriatic arthritis; CS = Control subjects.

Figure 3.

Serum levels of (a) IL-17A and (b) IL-17E according to psoriasis type in PsA patients. Horizontal lines indicate median and 25th–75th percentiles of the cytokine serum levels. Statistical analysis was performed using Kruskal–Wallis test.

Figure 4.

Positive correlations between serum levels of IL-31 and the Th17 cytokine profile in PsA patients. Correlation between serum levels of IL-31 with (a) IL-17A, (b) IL-17F, (c) IL-17E, (d) IL-21, and (e)IL-23 in PsA. r_s is Spearman’s correlation coefficient. GraphPad Prism v5.0 was used to create the figures.