Tehran University Medical Journal

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, involves almost all organs such as skin, heart, kidneys and central nervous system. The disease is characterized by vascular and connective tissue inflammation in a recurring pattern of remission and flare. Although the exact pathophysiology of disease has not been fully understood yet, the fundamental defect in SLE is attributed to dysfunction of T lymphocytes in controlling of B-cell that leads to polyclonal activation of B lymphocytes and production a large quantity of autoantibodies against nuclear and cytoplasmic components. These autoantibodies can damage tissues either directly or as a result of immune complex deposits. Several factors are involved in pathogenesis of SLE which can be divided into three major groups, environmental factors, genetic components, and immunological disturbances. They could breakdown body tolerance towards endogenous antigens and cause abnormal immunologic response to the healthy tissue, resulting in tissue damage. SLE occurs more frequently in female than male. It seems that immunological factors have important role in SLE. Inflammation and vascular endothelium irregularities are a number of main pathologies seen in SLE. Cytokines are protein mediators that play an essential role as regulator of innate and adaptive immune response against microbial agents or self-antigens. Influences of cytokines in autoimmune diseases such as SLE are poorly understood. Studies in both experimental animal models of lupus and patients with SLE have revealed a number of cytokine pathways that are important in the disease process. These studies showed that overexpression of inflammatory cytokines increases the proliferation of auto reactive B-cells and results in higher production of autoantibodies. Among them, the role of B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), TNF-α, IFN-α, IL-6, IFN-γ, IL-23/IL-17, IL-10, IL-21 are prominent, which is associated with the generation of pathogenic autoantibodies and formation of immune complexes. In this paper, the role of cytokines and their encoding genes are described, while therapeutic applications are also briefly presented.

Keywords: cytokines, pathogenesis, ligands, systemic lupus erythematosus

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