Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài:The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. | The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells Chang et al. Bk Med Central Chang et al. Arthritis Research Therapy 2011 13 R115 http content 13 4 R115 13 July 2011 Chang et al. Arthritis Research Therapy 2011 13 R115 http content 13 4 R115 RESEARCH ARTICLE Open Access The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells 1 1 11 1 Betty Y Chang Min Mei Huang Michelle Francesco Jun Chen Jeremy Sokolove Padmaja Magadala William H Robinson2 3 and Joseph J Buggy 1 Abstract Introduction The aim was to determine the effect of the Bruton tyrosine kinase Btk -selective inhibitor PCI-32765 currently in Phase I II studies in lymphoma trials in arthritis and immune-complex IC based animal models and describe the underlying cellular mechanisms. Methods PCI-32765 was administered in a series of murine IC disease models including collagen-induced arthritis CIA collagen antibody-induced arthritis CAIA reversed passive anaphylactic reaction RPA and passive cutaneous anaphylaxis PCA . Clinical and pathologic features characteristic of each model were examined following treatment. PCI-32765 was then examined in assays using immune cells relevant to the pathogenesis of arthritis and where Btk is thought to play a functional role. These included proliferation and calcium mobilization in B cells cytokine and chemokine production in monocytes macrophages degranulation of mast cells and its subsequent cytokine chemokine production. Results PCI-32765 dose-dependently and potently reversed arthritic inflammation in a therapeutic CIA model with an ED50 of mg kg day. PCI-32765 also prevented clinical arthritis in CAIA models. In both models infiltration of monocytes and macrophages into the synovium was completely inhibited and importantly the bone and cartilage integrity of the joints were preserved.
