Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum

Abstract

Background: Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects. Objectives: To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity. Methods: Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1b, IL6, IL8, tumour necrosis factor a, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28). Results: Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p,0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p,0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r = 0.53, p,0.02), and DAS28 (r = 0.44, p,0.05), but not with selected (adipo) cytokines. Conclusion:The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.

The role of resistin as a regulator of inflammation: Implications for various human pathologies

“…These authors observed an association of synovial fluid resistin with inflammatory markers of the disease. Moreover, the association between serum resistin levels, disease activity, and acute phase reactants, including C-reactive protein and IL-1Ra antagonizing IL-1β, suggests that resistin may be a significant mediator in the inflammatory process of RA [31,101]. On the contrary, serum resistin levels were comparable between patients with erosive and non-erosive hand osteoarthritis and were neither associated with signs of clinical nor laboratory markers of inflammation [102].…”

“…In contrast to mice, only a low level of expression of resistin has been found in mature adipocytes in humans [24][25][26][27]. In humans, resistin is highly expressed in the bone marrow compared to other tissues [28], but it is also present in trophoblastic cells of placenta, pancreas, primary cell leukemia, synovial fluid, synovial tissue, and circulating blood [22,24,[28][29][30][31][32][33][34]. The particular cells that express resistin in white adipose tissue are monocytes and macrophages [26,28,35].…”

“…Interestingly, injection of recombinant resistin into healthy mouse joints induces infiltration of the synovial tissue with leukocytes, which resembles the pathology of rheumatoid arthritis [36]. In general, the local production of resistin at sites of inflammation could be suggested of more importance, because it has been found in numerous resident and immune cell types within the hyperplastic rheumatic synovial tissue [30,31,[103][104][105][106].…”

Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases

“…There are demonstrations that resistin may also be involved in the pathogenesis of RA: resistin has been found in the plasma and the synovial fluid of RA patients, and injection of resistin into mice joints induces an arthritis-like condition, with leukocyte infiltration of synovial tissues, hypertrophy of the synovial layer, and pannus formation (Bokarewa et al 2005, Senolt et al 2007). However, plasma resistin levels in RA patients appear similar to those found in healthy controls and although in some studies of RA patients resistin levels were higher in synovial fluid than in serum (which shows that circulating levels of adipokines do not necessarily reflect the situation in the joint), the discrepancy may be due simply to the increased permeability of inflamed synovial membrane (Otero et al 2006, Schaffler et al 2003, Bokarewa et al 2005.…”

Resistin increases the expression of NOD2 in mouse monocytes

“…Previous studies have investigated the function of resistin in mouse obesity and diabetes models, and have implicated resistin in the pathogenesis of obesity-mediated insulin resistance and type 2 diabetes (3,12,13). Moreover, it has been reported that resistin is closely associated with inflammation (14)(15)(16). Resistin regulates the synthesis and secretion of proinflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and IL-1β in macrophages via a nuclear factor κB (NF-κB)-dependent pathway (17)(18)(19)(20), but the specific receptor of resistin in vivo has not yet been identified.…”