AB0110 ADIPONECTIN INDUCES PRO-INFLAMMATORY CHEMOKINE AND CYTOKINE PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS AND FIBROBLAST-LIKE SYNOVIOCYTES FROM NON-INFLAMED SUBJECTS
Authors: Y. Zhang, J. Aldridge, G. K. Vasileiadis, A. C. Lundell, A. Rudin, C. Maglio
Journal: Annals of the Rheumatic Diseases (2020)

Background: Adiponectin is a cytokine mainly secreted by the adipose tissue 1 , whose circulating levels are paradoxically low in subjects with obesity and associate with a beneficial metabolic profile 2 ., Recent studies have shown that adiponectin levels are elevated in both serum and synovial fluid collected from patients with rheumatoid arthritis (RA) 3,4 . Moreover, adiponectin is able to induce the production of interleukin (IL)-6, tumor necrosis factor (TNF), CXCL1 and CXCL8 by lymphocytes from healthy subjects 5 , and of IL-6 and CXCL8 by fibroblast-like synoviocytes (FLS) from patients with RA 6 . However, it is not clear if adiponectin is able to initiate the inflammatory processes associated with the preclinical phase of RA. Objectives: We aim to determine if adiponectin is able to induce inflammatory responses in peripheral blood mononuclear cells (PBMCs) and FLS from non-inflamed subjects. Methods: Human PBMCs were collected from healthy donors, whereas non-inflamed FLS from non-arthritic patients who underwent diagnostic arthroscopy due to previous trauma. PBMCs (1× 10 5 cells/well in 96-well plate) and FLS (5000 cells/well in 96-well plate) were stimulated using 5 μg/ml recombinant human total adiponectin protein, and the supernatants were collected 48 hours after stimulation. Phytohemagglutinin (PHA) and TNF were used as positive controls to activate PBMCs and FLS, respectively. Using multiplex assay and ELISA, we screened the production of 13 chemokines and 12 cytokines from healthy human PBMCs and non-inflamed FLS. Results: Adiponectin was able to stimulate a distinct profile of chemokines and cytokines in PBMCs and FLS. In both healthy PBMCs and non-inflamed FLS adiponectin induced the production of CXCL1, CXCL5, CXCL8, CCL2 and IL-6. Moreover, CCL3, CCL20, CCL4, CCL17, TNF, IL-10 and GM-CSF were induced by adiponectin only in healthy PBMCs, whereas CXCL10, CCL5 and CCL11 only in non-inflamed FLS (Fig. 1 and 2). Figure 1. Adiponectin induces the production of various chemokines from PBMCs (A) and FLS (B). CXCL8 (#) was measured using ELISA, and other chemokines were measured using multiplex assay. The fold change of CXCL1 in FLS (†) was not calculated because its level before stimulation was undetectable. Conclusion: We here report that adiponectin has pro-inflammatory properties as it induced chemokine and cytokine production from human healthy PBMCs and non-inflamed FLS. As adiponectin is able to induce pro-inflammatory responses from non-inflamed cells, we suggest that this adipokine might be implicated in the preclinical phase of RA pathogenesis. References: [1]Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013;2013:139239. [2]Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 2014;105:141-50. [3]Otero M, Lago R, Gomez R, et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:1198-201. [4]Schaffler A, Ehling A, Neumann E, et al. Adipocytokines in synovial fluid. JAMA 2003;290:1709-10. [5]Frommer KW, Zimmermann B, Meier FM, et al. Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis. Arthritis Rheum 2010;62:2886-99. [6]Kitahara K, Kusunoki N, Kakiuchi T, Suguro T, Kawai S. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts. Biochem Biophys Res Commun 2009;378:218-23. Figure 2. Adiponectin induces the production of IL-6 PBMCs (A) FLS (B) measured using ELISA. Disclosure of Interests: Yuan Zhang: None declared, Jonathan Aldridge: None declared, Georgios K. Vasileiadis: None declared, Anna-Carin Lundell: None declared, Anna Rudin Consultant of: Astra/Zeneca, Cristina Maglio: None declared