Rheumatoid Arthritis: Celik I

Ertenli I, Kiraz S, Oztürk MA, Haznedaroğlu I, Celik I, Calgüneri M. · Department of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey. · Rheumatol Int. · Pubmed #12634936 No free full text.

Abstract: Rheumatoid arthritis (RA) is frequently complicated by thrombocytosis correlated with disease activity. The exact pathogenetic mechanism(s) that cause increased platelet counts in RA are still unknown. Recent investigations indicate that proinflammatory pleiotropic cytokines of RA also have megakaryocytopoietic/thrombopoietic properties. Moreover, several lineage-dominant hematopoietic cytokines can also act as acute phase responders and contribute to the inflammation. This review focuses on the current literature and our experience regarding the dual relationships of the pathologic thrombopoiesis of RA. Growth factors contributing to it, namely interleukin (IL)-6, IL-11, stem cell factor, leukemia inhibitory factor, granulocyte colony stimulating factor, thrombopoietin (TPO), and the regulation of megakaryocytopoiesis during the inflammatory cascade are reviewed. Some data indicate that thrombopoietin could contribute to the reactive thrombocytosis of RA. In the non-lineage-specific gp130 cytokine family, IL-6 appears to predominate for the induction of megakaryopoiesis. However, other cytokines and growth factors may also contribute to the pathologic megakaryocytopoiesis of RA. Those pleiotropic mediators seem to act in concert to regulate this enigmatic process. Clarification of the pathobiologic basis of thrombopoiesis in RA may improve understanding of the disease pathogenesis and management of the inflammatory thrombocytosis.

Ertenli I, Kiraz S, Ertürk H, Haznedaroglu IC, Celik I, Calgüneri M, Kirazli S. · Department of Internal Medicine, Hacettepe University Medical School, Ankara, Turkey. · J Rheumatol. · Pubmed #10493673 No free full text.

Abstract: OBJECTIVE: To investigate circulating thrombopoietin (TPO) concentrations in systemic sclerosis (SSc). METHODS: TPO concentrations were measured by ELISA in serum samples of 13 patients (11 female, 2 male) with diffuse SSc, 15 healthy controls (13 female, 2 male), and 15 patients (13 female, 2 male) with rheumatoid arthritis (RA). Thrombocyte counts of patients with SSc and RA and controls were recorded. RESULTS: Median TPO concentrations were 115 (164) in SSc, 76 (32) in RA, and 62 (34) pg/ml in controls. Median serum TPO concentration in the SSc group was significantly higher than other groups; there was no difference between controls and patients with RA (p<0.001 for both comparisons). Median platelet counts of SSc, RA, and controls were 224+/-58x10(9)/l, 238+/-44x10(9)/l, and 272+/-35x10(9)/l, respectively. There was no correlation between thrombocyte counts and TPO levels in any group. CONCLUSION: We show that patients with SSc have higher serum TPO concentrations compared to healthy controls and patients with RA. It can be hypothesized that TPO mediated release of particular growth factors may participate in the pathogenesis of the fibrotic process of SSc.

Oztürk MA, Ertenli I, Kiraz S, C Haznedaroğlu I, Celik I, Kirazli S, Calgüneri M. · Department of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey. · Rheumatol Int. · Pubmed #12750940 No free full text.

Abstract: Behçet's disease (BD) commonly presents with articular manifestations and thrombotic vasculopathy. Arthritis of BD characteristically demonstrates a recurrent and nondestructive course. The pathobiological basis of the thrombotic vasculopathy and protective factors against cartilage destruction in arthritis of BD have not been elucidated. Apart from being involved in fibrinolysis and thrombolysis, the plasminogen activation system can contribute to the pathogenesis of destructive joint diseases such as rheumatoid arthritis (RA). Plasminogen activator inhibitor-1 (PAI-1) is a well known fibrinolysis inhibitor. In this study, local synovial fluid and circulating plasma PAI-1 concentrations of BD were assessed in comparison to RA patients and healthy controls to investigate the nonerosive, nondestructive nature of Behçet arthritis. Twelve patients with BD (mean age 34+/-11 years, males:females 6:6), 15 with RA (mean age 36+/-8 years, males:females 3:12), and 15 healthy adults (mean age 32+/-10 years, males:females 6:9) were included in this study. Plasma PAI-1 antigen levels and PAI-1 activities were significantly greater in BD patients than in RA patients and healthy controls ( P<0.001). Synovial fluid levels of both parameters were also higher than in RA patients ( P<0.001). These results suggest that PAI-1 may promote hypofibrinolysis of Behçet's vasculopathy and also have a protective role in the arthritis of BD.

Kiraz S, Ertenli I, Oztürk MA, Haznedaroğlu IC, Celik I, Kirazli S, Calgüneri M. · Hacettepe University School of Medicine, Ankara, Turkey. · Clin Rheumatol. · Pubmed #12447626 No free full text.

Abstract: Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO may also act as an acute-phase reactant, and it has been suggested as a component of inflammatory reactions. In this study our objective was to investigate serum TPO levels in patients with rheumatoid arthritis, a complex chronic inflammatory disorder not uncommonly associated with thrombocytosis. Bloodstream TPO concentrations were assessed in 13 RA patients with platelet counts between 450 and 650 x 10(9)/l, 10 RA patients with platelet counts >650 x 10(9)/l, 15 RA patients with normal platelet counts and 12 healthy controls. RA patients with normal platelet counts had TPO levels comparable with healthy controls. TPO concentrations in patients with mild thrombocytosis were significantly elevated, whereas patients with markedly increased thrombocyte counts had prominently decreased TPO levels. These results indicate that TPO seems to be associated with reactive thrombocytosis in RA patients with active disease. In patients with extremely increased thrombocytosis serum TPO levels might be regulated by increased platelet mass via receptor-mediated uptake and metabolism.

Ertenli I, Kiraz S, Calgüneri M, Celik I, Erman M, Haznedaroglu IC, Kirazli S. · Department of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey. · Clin Exp Rheumatol. · Pubmed #11760396 No free full text.

Abstract: OBJECTIVE: To investigate the synovial fluid levels of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-1 receptor antagonist (IL-1ra), soluble IL-2 receptor (sIL-2r) and IL-8 in patients with Behçet's disease (BD) and to compare them to levels in rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: The cytokine levels of BD (n = 14), RA (n = 15) and OA (n = 15) patients were assessed by enzyme-linked immunosorbent method. RESULTS: Median synovial IL-1 beta and TNF-alpha levels were higher in RA compared to BD and OA patients. IL-1 beta levels were also higher in BD than OA whereas TNF levels were similar in these two groups. IL-1ra and TGF-beta activity in BD were higher than OA but lower than RA. sIL-2r and IL-8 levels were increased in BD and RA in comparison to OA patients. CONCLUSION: The arthritis of BD is non-erosive and accordingly, its synovial fluid contains lower levels of cytokines primarily involved in cartilage destruction, namely IL-1 beta and TNF-alpha, than RA. IL-1ra and TGF might serve as protective factors against erosion in the inflamed joints. High synovial fluid levels of sIL-2r and IL-8 probably reflect a non-specific inflammatory process.