Apart from patients with RA, increased IL7 levels are found in the blood circulation or at the inflammatory site of several other (auto) immune\mediated diseases, such as psoriasis and JIA.22,39 Since in these diseases anti\TNF treatment is used as an anti\inflammatory drug and IL7 may be an important proinflammatory mediator, detailed analysis of the role of IL7 in the immunopathogenesis of RA and these diseases may lead to novel treatment strategies. Acknowledgements We thank Dr Nazira Jahangier and Dr Andre van Rijthoven for providing patient material, and Dr D Fitzpatrick and Dr C Willis (Amgen) for critical reading of the manuscript. TNF levels in RA synovial fluid and synovial tissue significantly correlated. IL7\stimulated Albiglutide lymphocyte responses were not inhibited by TNF blockade. Mouse monoclonal to EphA4 Circulating IL7 levels were significantly reduced in patients who successfully responded to anti\TNF treatment. However, IL7 levels persisted in non\responders. Conclusion The present data suggest that IL7 is an important inducer of T cell\dependent TNF production in RA joints. This may contribute to the correlation Albiglutide of intra\articular IL7 and TNF in these joints. Furthermore, the persistence of IL7\induced inflammatory activity on TNF blockade in vitro and persistence of IL7 levels and disease activity in anti\TNF non\responders suggest that IL7 might additionally promote TNF\impartial inflammation. Rheumatoid arthritis (RA) is a chronic disabling type of arthritis that affects 1% of the adult populace. RA is usually characterised by prolonged inflammation of the joints, often resulting in constantly progressing tissue destruction. 1 Numerous studies revealed a pivotal role for CD4 T cells and macrophages in RA synovitis2,3,4,5,6 associated with the abundant production of catabolic enzymes and proinflammatory cytokines,2,7 including tumour necrosis factor (TNF).8,9,10,11,12,13,14,15 Clinical studies have supported the importance of TNF in the inflammatory and tissue\destructive processes in patients with RA.16 Despite the success of anti\TNF treatment, a considerable number of patients do not respond or only improve partially.16,17,18 The lack of efficacy of anti\TNF treatment in certain patients might be due to persisting TNF\independent proinflammatory activity induced by mediators other than TNF. Additionally, such mediators may contribute to continuous induction of TNF, preventing an adequate response to anti\TNF treatment. Recently, several studies indicated that interleukin (IL)7 might be such a mediator, contributing to chronic inflammation in RA. IL7 belongs to the IL2 family of cytokines that includes IL2, IL4, IL9, IL15, IL21 and thymic stromal lymphopoietin. IL7 mediates its effects through the IL7R, which consists of the common cytokine chain (c) and the IL7R chain.19 IL7 is produced by stromal cells at lymphopoietic sites and plays a role in the regulation of peripheral homeostasis of the CD4 T cell pool. IL7 is usually a growth factor for T cells in early T cell development, and promotes proliferation, survival and differentiation of mature naive and memory T cells.20 In addition, high concentrations of IL7 were shown to induce cytokine production by monocytes from healthy individuals.21 In patients with arthritis (RA and juvenile idiopathic arthritis (JIA)), increased levels of IL7 have been shown compared with healthy controls22,23,24 and correlated with increased disease activity.22,24 In addition, recently, strongly increased IL7 levels were found in the synovial fluid (SF) of patients with RA and patients with JIA compared with patients with osteoarthritis and oligoarticular patients, respectively.25,26 Furthermore, abundant expression of IL7 by macrophages, endothelial cells and fibroblasts was detected in the synovial tissue of patients with RA.25,27 The purpose of this study was to define the mechanism by which IL7 induces TNF production by monocytes and CD4 T cells, and to investigate the relationship between intra\articular IL7 and TNF levels. The TNF dependency of IL7\induced lymphocyte activation was tested in vitro by TNF blockade. Finally, the persistence of IL7 levels on TNF blockade was analyzed in patients treated with the anti\TNF monoclonal antibody adalimumab. Methods Patients Table 1?1 Albiglutide shows the demography of patients with RA. Patients with RA were classified according to the 1987 revised American College of Rheumatology criteria.28 Patients who donated peripheral blood (PB) or synovial fluid for cell cultures or analysis of IL7 and TNF by ELISA were.