Cytokine Disturbances in Systemic Lupus Erythematosus
Cytokine Disturbances in Systemic Lupus Erythematosus
The pathogenesis of systemic lupus erythematosus (SLE) is complex, and the resulting disease manifestations are heterogeneous. Cytokine dysregulation is pervasive, and their protein and gene expression profiles may serve as markers of disease activity and severity. Importantly, biologic agents that target specific cytokines may represent novel therapies for SLE. Four cytokines (IL-6, TNFα, IFNα, and BLyS) are being evaluated as therapeutic targets in SLE. The present review will examine the roles of each of these cytokines in murine and human SLE, and will summarize results from clinical trials of agents that target these cytokines.
Cytokines collectively play key roles in the regulation of systemic inflammation, local tissue damage, and immunomodulation. Not surprisingly, cytokines often play direct roles in disease pathogenesis, including that of systemic lupus erythematosus (SLE). To the chagrin of both investigator and practitioner, the effects of cytokines are pleiotropic and include both synergistic and antagonistic effects on other cytokines - thereby introducing tremendous complexity that has often led to diametrically opposing conclusions in different studies. In the present review, we focus on four cytokines that have received great attention either as candidate biomarkers for disease activity and/or as candidate targets of novel biologic agents.
Abstract and Introduction
Abstract
The pathogenesis of systemic lupus erythematosus (SLE) is complex, and the resulting disease manifestations are heterogeneous. Cytokine dysregulation is pervasive, and their protein and gene expression profiles may serve as markers of disease activity and severity. Importantly, biologic agents that target specific cytokines may represent novel therapies for SLE. Four cytokines (IL-6, TNFα, IFNα, and BLyS) are being evaluated as therapeutic targets in SLE. The present review will examine the roles of each of these cytokines in murine and human SLE, and will summarize results from clinical trials of agents that target these cytokines.
Introduction
Cytokines collectively play key roles in the regulation of systemic inflammation, local tissue damage, and immunomodulation. Not surprisingly, cytokines often play direct roles in disease pathogenesis, including that of systemic lupus erythematosus (SLE). To the chagrin of both investigator and practitioner, the effects of cytokines are pleiotropic and include both synergistic and antagonistic effects on other cytokines - thereby introducing tremendous complexity that has often led to diametrically opposing conclusions in different studies. In the present review, we focus on four cytokines that have received great attention either as candidate biomarkers for disease activity and/or as candidate targets of novel biologic agents.
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