Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 10; pp. 19588 - 19604
• Main Authors: Chu, Man, Wong, Chun, Cai, Zhe, Dong, Jie, Jiao, Delong, Kam, Ngar, Lam, Christopher, Tam, Lai
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.10.2015; MDPI
• Subjects: Adult; B-Lymphocytes, Regulatory - metabolism; Cross-Sectional Studies; Cytokines; Disease; Female; Gene Expression Regulation; Humans; IL-36; Interleukin-1 - blood; Interleukin-10 - blood; Interleukin-6 - blood; Interleukin-8 - blood; Investigations; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Lymphocytes; Male; Medicine; Middle Aged; Plasma; Receptors, Interleukin - blood; regulatory B lymphocytes; systemic lupus erythematosus; Up-Regulation; Young Adult; Hong Kong China; United Kingdom > UK; China; Wales; Macao; regulatory B lymphocytes; systemic lupus erythematosus; IL-36; cytokines
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules201019588

We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19+CD24highCD27+ regulatory B (Breg) lymphocytes of peripheral blood from 43 SLE patients and 16 normal control (NC) subjects were studied using ELISA and flow cytometry. Plasma cytokines/chemokines and ex vivo productions of cytokine/chemokine from peripheral blood mononuclear cells (PBMC) stimulated with recombinant IL-36 were determined by Luminex multiplex assay. Plasma concentrations of IL-36α, IL-36γ and the proportions of circulating IL-36R-positive CD19+ B lymphocytes in total B lymphocytes and PBMC were significantly increased in active SLE patients compared with NC (all p < 0.05). Plasma IL-36α and IL-36γ correlated positively with SLE disease activity and elevated plasma IL-10 concentration (all p < 0.05). The frequencies of circulating Breg lymphocytes in total B lymphocytes and PBMC were significantly decreased in both inactive and active SLE patients compared with NC (all p < 0.01). The frequency of Breg lymphocytes in total B lymphocytes correlated negatively with the proportion of IL-36R-positive B lymphocytes (p < 0.05). IL-36α exerted substantial proinflammatory effect in PBMC from SLE patients by inducing the production of IL-6 and CXCL8. Upon stimulation with IL-36α and IL-36γ, ex vivo productions of IL-6 and CXCL8 were significantly increased in SLE patients compared with NC (all p < 0.05). This cross-sectional study demonstrated that over expression of circulating IL-36α may exert a proinflammatory effect as observed in human SLE.