Circulating levels of the chemokine CCL18 but not CXCL16 are elevated and correlate with disease activity in rheumatoid arthritis

Background: Antigen-presenting cells (APC) and T cells are considered to play a significant role in the pathogenesis of rheumatoid arthritis (RA). CCL18 and CXCL16 are two chemokines that facilitate T cell attraction by APC, of which a role in the pathogenesis of RA has been suggested. Objective: To compare the circulating levels of CXCL16 and CCL18 in RA with controls and to investigate the relation of CXCL16 and CCL18 with RA disease activity and joint damage. Methods: Circulating CCL18 and CXCL16 levels were determined in 61 RA patients with a follow-up of 6 years and a group of 41 healthy controls with ELISA. Chemokine levels were correlated with demographic data, disease activity (DAS28) and joint damage (modified Sharp score). In addition, serum CCL18 and CXCL16 levels from a cohort of 44 RA patients treated with anti-TNF-α were correlated with disease activity. Results: CCL18 levels in serum were significantly elevated in RA patients compared with controls, while serum CXCL16 levels were not. In contrast to CXCL16, serum CCL18 was positively correlated with disease activity. Both CCL18 and CXCL16 levels decreased upon treatment with anti-TNF-α. Neither CCL18 nor CXCL16 correlated with joint damage and progression. Conclusion: Here, we show, for the first time, that circulating CCL18 and not CXCL16 levels are elevated in RA patients as compared with controls and correlate with disease activity in RA. More knowledge regarding the regulation and function of both CCL18 and CXCL16 is essential to value their role in RA.

[1]  B. W. Schreurs,et al.  Novel insights in the regulation of CCL18 secretion by monocytes and dendritic cells via cytokines, Toll-like receptors and rheumatoid synovial fluid , 2006, BMC Immunology.

[2]  B. Wallaert,et al.  Involvement of CCL18 in Allergic Asthma1 , 2006, The Journal of Immunology.

[3]  Marcel M. Verbeek,et al.  CXCL16 is elevated in the cerebrospinal fluid versus serum and in inflammatory conditions with suspected and proved central nervous system involvement , 2006, Neuroscience Letters.

[4]  G. Haines,et al.  CXCL16-mediated cell recruitment to rheumatoid arthritis synovial tissue and murine lymph nodes is dependent upon the MAPK pathway. , 2006, Arthritis and rheumatism.

[5]  N. Miyasaka,et al.  Pathogenic role of the CXCL16-CXCR6 pathway in rheumatoid arthritis. , 2005, Arthritis and rheumatism.

[6]  M. Hasegawa,et al.  Serum pulmonary and activation-regulated chemokine/CCL18 levels in patients with systemic sclerosis: a sensitive indicator of active pulmonary fibrosis. , 2005, Arthritis and rheumatism.

[7]  N. Ohkohchi,et al.  Cutting Edge: Critical Role of CXCL16/CXCR6 in NKT Cell Trafficking in Allograft Tolerance 1 , 2005, The Journal of Immunology.

[8]  N. Kadowaki,et al.  Distribution and kinetics of SR‐PSOX/CXCL16 and CXCR6 expression on human dendritic cell subsets and CD4+ T cells , 2005, Journal of leukocyte biology.

[9]  C. Figdor,et al.  Elevated CXCL16 expression by synovial macrophages recruits memory T cells into rheumatoid joints. , 2005, Arthritis and rheumatism.

[10]  C. Figdor,et al.  Novel monoclonal antibodies detect elevated levels of the chemokine CCL18/DC‐CK1 in serum and body fluids in pathological conditions , 2005, Journal of Leukocyte Biology.

[11]  W. Fridman,et al.  CC Chemokine Ligand 18, An Atopic Dermatitis-Associated and Dendritic Cell-Derived Chemokine, Is Regulated by Staphylococcal Products and Allergen Exposure1 , 2004, The Journal of Immunology.

[12]  C. Figdor,et al.  Increased expression of CCL18, CCL19, and CCL17 by dendritic cells from patients with rheumatoid arthritis, and regulation by Fc gamma receptors , 2004, Annals of the rheumatic diseases.

[13]  P. V. van Riel,et al.  Inhibition of TNFα during maturation of dendritic cells results in the development of semi-mature cells: a potential mechanism for the beneficial effects of TNFα blockade in rheumatoid arthritis , 2004, Annals of the rheumatic diseases.

[14]  S. Rose-John,et al.  The Transmembrane CXC-Chemokine Ligand 16 Is Induced by IFN-γ and TNF-α and Shed by the Activity of the Disintegrin-Like Metalloproteinase ADAM10 1 , 2004, The Journal of Immunology.

[15]  P. Dempsey,et al.  A Disintegrin and Metalloproteinase 10-Mediated Cleavage and Shedding Regulates the Cell Surface Expression of CXC Chemokine Ligand 16 , 2004, The Journal of Immunology.

[16]  T. Kita,et al.  Cell surface‐anchored SR‐PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6‐expressing cells , 2004, Journal of leukocyte biology.

[17]  G. Opdenakker,et al.  PARC/CCL18 is a plasma CC chemokine with increased levels in childhood acute lymphoblastic leukemia. , 2003, The American journal of pathology.

[18]  T. Kita,et al.  Cutting Edge: SR-PSOX/CXC Chemokine Ligand 16 Mediates Bacterial Phagocytosis by APCs Through its Chemokine Domain1 , 2003, The Journal of Immunology.

[19]  S. Jimenez,et al.  Pulmonary and activation-regulated chemokine stimulates collagen production in lung fibroblasts. , 2003, American journal of respiratory cell and molecular biology.

[20]  Osamu Yoshie,et al.  Cutting Edge: Profile of Chemokine Receptor Expression on Human Plasma Cells Accounts for Their Efficient Recruitment to Target Tissues 1 , 2003, The Journal of Immunology.

[21]  P. Allavena,et al.  Identification of Biologically Active Chemokine Isoforms from Ascitic Fluid and Elevated Levels of CCL18/Pulmonary and Activation-regulated Chemokine in Ovarian Carcinoma* , 2002, The Journal of Biological Chemistry.

[22]  G. Opdenakker,et al.  Selective induction of CCL18/PARC by staphylococcal enterotoxins in mononuclear cells and enhanced levels in septic and rheumatoid arthritis , 2001, European journal of immunology.

[23]  D. Soler,et al.  Expression Cloning of the STRL33/BONZO/TYMSTR Ligand Reveals Elements of CC, CXC, and CX3C Chemokines , 2001, The Journal of Immunology.

[24]  C. Figdor,et al.  The Dendritic Cell-Specific CC-Chemokine DC-CK1 Is Expressed by Germinal Center Dendritic Cells and Attracts CD38-Negative Mantle Zone B Lymphocytes , 2001, The Journal of Immunology.

[25]  T. Kita,et al.  Molecular Cloning of a Novel Scavenger Receptor for Oxidized Low Density Lipoprotein, SR-PSOX, on Macrophages* , 2000, The Journal of Biological Chemistry.

[26]  Sharon Engel,et al.  A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo , 2000, Nature Immunology.

[27]  P. Lipsky,et al.  Infliximab (chimeric anti-tumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial , 1999, The Lancet.

[28]  Z Domljan,et al.  Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. , 1998, Arthritis and rheumatism.

[29]  S. Goerdt,et al.  Alternative macrophage activation-associated CC-chemokine-1, a novel structural homologue of macrophage inflammatory protein-1 alpha with a Th2-associated expression pattern. , 1998, Journal of immunology.

[30]  Jonathan M. Austyn,et al.  Dendritic cells , 1998, Current opinion in hematology.

[31]  Y. Sakaki,et al.  A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes. , 1997, Journal of immunology.

[32]  T. Mcclanahan,et al.  A dendritic-cell-derived C–C chemokine that preferentially attracts naive T cells , 1997, Nature.

[33]  W. B. Berg,et al.  The role of macrophages in chronic arthritis. , 1996 .

[34]  M. Cutolo,et al.  Macrophages, synovial tissue and rheumatoid arthritis. , 1993, Clinical and experimental rheumatology.

[35]  F. Arnett.  Revised criteria for the classification of rheumatoid arthritis. , 1990, Orthopedic nursing.

[36]  D. Heijde,et al.  EFFECTS OF HYDROXYCHLOROQUINE AND SULPHASALAZINE ON PROGRESSION OF JOINT DAMAGE IN RHEUMATOID ARTHRITIS , 1989, The Lancet.

[37]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[38]  Boris Bleijlevens,et al.  Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention. , 2004, Blood.

[39]  Ranjeny Thomas.  Antigen-presenting cells in rheumatoid arthritis , 2004, Springer Seminars in Immunopathology.

[40]  W. B. van den Berg,et al.  The role of macrophages in chronic arthritis. , 1996, Immunobiology.

[41]  M. Prevoo,et al.  Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. , 1995, Arthritis and rheumatism.