Abstract
BackgroundChemerin is a specific chemoattractant for macrophages and dendritic cells (DC). In addition, it can rapidly stimulate macrophage adhesion to extracellular matrix proteins and adhesion molecules and is able to activate fibroblast-like synoviocytes (FLS), suggesting a role in the pathogenesis of rheumatoid arthritis (RA). Chemerin is also an adipocytokine that has been related to the inflammatory state of endothelial cells and as such could be involved in the changes in endothelial cells in RA and perhaps increased cardiovascular morbidity. We investigated whether anti-Tumor Necrosis Factor (TNF) treatment affects chemerin levels.Materials and Methods49 patients with active RA (disease activity score evaluated in 28 joints (DAS28) ≥3.2) were started on adalimumab therapy. Blood was drawn from patients while fasting at baseline and 16 weeks after initiation of treatment. Chemerin serum levels were measured by ELISA and related to disease activity, mediators of inflammation and known risk factors for cardiovascular disease.ResultsAdalimumab therapy reduced chemerin serum levels, which was correlated with the reduction in DAS28 (r = 0.37, p = 0.009). In addition, the decrease in chemerin serum levels after anti-TNF treatment was associated with the decrease in serum levels of IL-6 (r = 0.39, p = 0.033) and macrophage migration inhibitory factor (MIF) (r = 0.31, p = 0.049). Baseline chemerin serum levels were not related to traditional risk factors for atherosclerosis, except perhaps for smoking (p = 0.07).ConclusionsThis exploratory study shows that adalimumab therapy lowers chemerin levels, which is associated with the reduction in disease activity parameters, and inflammatory mediators IL-6 and MIF. This suggests a possible involvement of chemerin in the migration/retention of macrophages in the synovium.Trial Registration Nederlands Trial Register NTR 857
Highlights
Adalimumab therapy reduced chemerin serum levels, which was correlated with the reduction in DAS28 (r = 0.37, p = 0.009)
The decrease in chemerin serum levels after anti-Tumor Necrosis Factor (TNF) treatment was associated with the decrease in serum levels of IL-6 (r = 0.39, p = 0.033) and macrophage migration inhibitory factor (MIF) (r = 0.31, p = 0.049)
This exploratory study shows that adalimumab therapy lowers chemerin levels, which is associated with the reduction in disease activity parameters, and inflammatory mediators IL-6 and MIF
Summary
The synovium in rheumatoid arthritis (RA) is characterized by a dense infiltrate, consisting of T and B cells, plasma cells, macrophages, dendritic cells (DC), and other cells. [1] Inflammatory chemokines present in the synovium contribute to the migration and/or retention of these immune cells.[2,3,4] Chemerin is a recently discovered chemokine that modulates chemotaxis and activation of macrophages and DC (in particular plasmacytoid DC (pDC) and monocyte-derived DC). [5] it can contribute to inflammation by stimulating macrophage adhesion to extracellular matrix proteins and adhesion molecules. [6] The expression of chemerin receptor chemokinelike receptor 1 (CMKLR1) or ChemR23 on antigen-presenting cells (macrophages and DC) suggests that chemerin constitutes an important link between innate and adaptive immunity. [6] The expression of chemerin receptor chemokinelike receptor 1 (CMKLR1) or ChemR23 on antigen-presenting cells (macrophages and DC) suggests that chemerin constitutes an important link between innate and adaptive immunity Both the innate and adaptive immune responses are implicated in the pathogenesis of RA and might even occur in a parallel fashion. Related to this it was recently reported [7] in RA that endothelial cells and synovial lining and sublining cells express chemerin while its receptor ChemR23 was expressed on macrophages, immature DCs and fibroblast-like synoviocytes (FLS). We investigated whether anti-Tumor Necrosis Factor (TNF) treatment affects chemerin levels
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