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Chronic inflammation underlies the pathological progression of various diseases, and thus many efforts have been made to quantitatively evaluate the inflammatory status of the diseases. In this study, we generated a highly sensitive inflammation-monitoring mouse system using a bacterial artificial chromosome (BAC) clone containing extended flanking sequences of the human interleukin 6 gene (hIL6 ) locus, in which the luciferase (Luc) reporter gene is integrated (hIL6 -BAC-Luc ). We successfully monitored lipopolysaccharide-induced systemic inflammation in various tissues of thehIL6 -BAC-Luc mice using anin vivo bioluminescence imaging system. When two chronic inflammatory disease models, i.e., a genetic model of atopic dermatitis and a model of experimental autoimmune encephalomyelitis (EAE), were applied to thehIL6 -BAC-Luc mice, luciferase bioluminescence was specifically detected in the atopic skin lesion and central nervous system, respectively. Moreover, the Luc activities correlated well with the disease severity. Nrf2 is a master transcription factor that regulates antioxidative and detoxification enzyme genes. Upon EAE induction, the Nrf2-deficient mice crossed with thehIL6 -BAC-Luc mice exhibited enhanced neurological symptoms concomitantly with robust luciferase luminescence in the neuronal tissue. Thus, whole-bodyin vivo monitoring using thehIL6 -BAC-Luc transgenic system (WIM-6 system) provides a new and powerful diagnostic tool for real-timein vivo monitoring of inflammatory status in multiple different disease models.

Whole-Body In Vivo Monitoring of Inflammatory Diseases Exploiting Human Interleukin 6-Luciferase Transgenic Mice