title: Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus.
abstract: 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⁺CD24(high)CD27⁺ 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.
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. shaanxichuman@gmail.com.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. shaanxichuman@gmail.com.
authors.forename: Man
authors.initials: M
authors.lastname: Chu
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. ck-wong@cuhk.edu.hk.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. ck-wong@cuhk.edu.hk.|State Key Laboratory of Phytochemistry and Plant Resources in West China, Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China. ck-wong@cuhk.edu.hk.
authors.forename: Chun Kwok
authors.initials: CK
authors.lastname: Wong
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. caifranklin@163.com.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. caifranklin@163.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. dongjie0805@163.com.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. dongjie0805@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China. j.dl@foxmail.com.|Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. j.dl@foxmail.com.
authors.forename: Delong
authors.initials: D
authors.lastname: Jiao
authors.affiliation: Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. yvonne_kam@yahoo.com.hk.|Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. yvonne_kam@yahoo.com.hk.
authors.forename: Ngar Woon
authors.initials: NW
authors.lastname: Kam
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau. wklam@must.edu.mo.
authors.forename: Christopher Wai Kei
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen 518057, China. lstam@cuhk.edu.hk.|Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. lstam@cuhk.edu.hk.
authors.forename: Lai Shan
authors.initials: LS
authors.lastname: Tam
mesh_terms: D000328:Adult; D060151:B-Lymphocytes, Regulatory / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D018123:Receptors, Interleukin; C572887:interleukin 36, human; C571244:interleukin-36 receptor, human; D016753:Interleukin-10
keywords: IL-36; cytokines; regulatory B lymphocytes; systemic lupus erythematosus