IL-18 in autoimmunity. Studies in autoimmune murine lupus and in human SLE

The chronic progressive lupus-like disease of lpr mice strongly involves Th1-dependent immune activation. Expression of the Th1-related cytokine IL-18 and of its receptors is greatly enhanced in lpr lymphoid organs early in life, well before pathology development. Hyper-expression of the Th2-activating IL-18-like cytokine IL-33 was evident in lpr mice, in parallel to increase of receptor expression. Expression of IL-17, present in normal organs, was undetectable in lpr mice. Thus, autoimmune pathogenesis in murine lupus correlates with up-regulation of Th1 and Th2 responses, with no involvement of Th17 reactions. In human lupus patients, serum and urine levels of IL-18 and its inhibitor IL-18BP were higher than in controls. However, only serum levels of IL-18BP positively correlated with disease severity (ECLAM score).