Abstract
The role of IL-18 in the pathogenesis of systemic lupus erythematosus is still not definitively solved. In this study, we generated MRLlpr mice, which develop a disease resembling systemic lupus erythematosus, genetically devoid of IL-18 expression. These mice in comparison to IL-18-competent MRLlpr mice show reduced signs of renal pathogenesis, while other parameters such as mean survival time, lymphadenopathy, constitutive interferon-γ production, and frequency of CD3+B220+ abnormal T cells were without differences. We conclude that in the systemic lupus erythematosus syndrom IL-18 is involved specifically in the renal pathogenesis.
Highlights
The interleukin (IL)-1 family member IL-18, originally referred to as ‘interferon (IFN)-γinducing factor (IGIF)’, is a proinflammatory cytokine [1]
In order to analyze a possible role of IL-18 in the pathogenesis of the lupus-like disease in MRL/Mp-Tnfrs6lpr (MRLlpr) mice, we intensively backcrossed the Il18tm/tmAki genotype from C57BL/6 mice onto the MRLlpr strain to obtain MRL/Mp-Tnfrs6lprIl18tm/tm (MRLlprIL18tm/tm) and MRL/Mp-Tnfrs6lprIl18+/tm (MRLlprIL18+/tm) mice
Several studies point to a contribution of IL-18 to symptoms associated with human lupus and the lupus-like disease in mouse models [7, 35,36,37,38]
Summary
The interleukin (IL)-1 family member IL-18, originally referred to as ‘interferon (IFN)-γinducing factor (IGIF)’, is a proinflammatory cytokine [1]. IL-18 by itself does not induce IFN-γ expression, but rather acts synergistically with e.g. IL-12, which induces expression of the IL-18 receptor [5, 6]. The participation of IL-18 in inflammatory diseases including autoimmunity has been demonstrated in several animal models and in humans [7,8,9]. SLE is characterized by hyper-gammaglobulinemia, autoantibody production and immune complex formation, eventually leading to end-organ damage, including vasculitis and fatal renal failure [10]. In plasma of SLE patients the concentration of IL-18 is enhanced and correlates with the disease activity [14,15,16]
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