Systemic lupus erythematosus (SLE) is usually a chronic autoimmune disease that is characterized by a defect in immune tolerance and exacerbated by both the innate and adaptive arms of the immune response. pathogenesis. Recent therapeutic strategies have focused on proximal cytokines such as interferon-α interleukin (IL)-1 IL-6 and tumor necrosis factor as a result of the efficacious use of biologic brokers for intervention in rheumatoid arthritis and other autoimmune diseases. Despite the recent improvements in understanding the cytokine networks involved in autoimmune diseases and more specifically in SLE the diagnosis and prognosis of lupus remain a challenge. Lupus is usually heterogeneous and unpredictable; moreover the frequency and severity of flares can be hard to determine and treat. A better understanding of the regulation of expression of key cytokines and their receptors can likely provide important clues to the pathogenic mechanisms underlying specific forms of SLE and pave the way toward more effective therapeutics. Introduction Systemic lupus erythematosus (SLE) is usually a chronic inflammatory disease that can result in skin rashes arthritis leukopenia nephritis and inflammation of the nervous system. This process begins with the loss of tolerance and the presence of autoreactive lymphocytes in the periphery as the result of the combination of both environmental and genetic factors (Kumar as well as others 2006; Crow 2008). Multiple cell types in the adaptive and innate Complanatoside A arms of the immune system have been documented to contribute to Complanatoside A lupus pathogenesis either Complanatoside A systemically or in the end organs. One of the pathogenomic features of SLE is the elaboration of anti-DNA and related antinuclear autoantibodies. Hence not surprisingly T cell-dependent B cell autoantibody production lies at the heart of disease pathogenesis. Thus cytokines that activate B and T cells and promote their conversation constitute important disease drivers. In addition it has become obvious that cells in the innate arm of the immune system play a key role in activating autoreactive lymphocytes in SLE. Although mechanisms have yet to be fully resolved early work exhibited that blood plasmacytoid dendritic cells (pDC) the primary suppliers of interferon (IFN)-α were decreased in the blood and recruited to inflamed tissues of SLE patients. The pDC through IFN-α secretion induced monocytes to become potent antigen presenting myeloid DC (mDC) (Blanco as well as others 2001). It was hypothesized that mDC rapidly captured apoptotic cells and nucleosomes and offered autoantigens to CD4+ T cells that became activated and underwent proliferation and clonal growth in the secondary lymphoid organs. Subsequently B lymphocytes stimulated by interactions with autoreactive CD4+ T cells and mDC produced autoantibodies. The autoantibodies in turn formed immune complexes with neutrophil products and components of nucleosomes HESX1 and directly stimulated toll like receptors (TLR) on pDC which were stimulated to secrete more IFN-α thereby propagating the inflammatory response. As depicted in Fig. 1 besides the systemic events an additional series of events takes place in Complanatoside A the end Complanatoside A organ (eg kidney) once Complanatoside A autoreactive lymphocytes myeloid cells and autoantibodies infiltrate into the target tissues. Attracted by cytokines and chemokines produced in the inflamed target tissues autoimmune lymphocytes respond with the elaboration of cytokines. Autoantibodies deposited in the target tissues as immune complexes further activate infiltrating myeloid cells and also the resident cells of the target tissue and perpetuate cytokine production along with release of destructive mediators such as reactive oxygen species prostaglandins and nitric oxide (Fu as well as others 2005; Fairhurst as well as others 2009). The producing tissue inflammation eventually causes fibrotic tissue and the more ominous clinical manifestations of the disease. Several of the cytokines that have been implicated in SLE pathogenesis are diagramed in Fig. 1. The aim of this article is usually to review our current understanding of these cytokines in the context of lupus pathogenesis and the potential for intervention with anticytokine therapies. FIG. 1. The role of cytokines in systemic and end-organ autoimmune-initiated interactions in.