Functional imaging of interleukin 1 beta expression in inflammatory process using bioluminescence imaging in transgenic mice.

Background: Interleukin 1 beta (IL-1beta) plays an important role in a number of chronic and acute inflammatory diseases. To understand the role of IL-1beta in disease processes and develop an in vivo screening system for anti-inflammatory drugs, a transgenic mouse line was generated which incorporated the transgene firefly luciferase gene driven by a 4.5-kb fragment of the human IL-1beta gene promoter. Luciferase gene expression was monitored in live mice under anesthesia using bioluminescence imaging in a number of inflammatory disease models.

Results: In a LPS-induced sepsis model, dramatic increase in luciferase activity was observed in the mice. This transgene induction was time dependent and correlated with an increase of endogenous IL-1beta mRNA and pro-IL-1beta protein levels in the mice. In a zymosan-induced arthritis model and an oxazolone-induced skin hypersensitivity reaction model, luciferase expression was locally induced in the zymosan injected knee joint and in the ear with oxazolone application, respectively. Dexamethasone suppressed the expression of luciferase gene both in the acute sepsis model and in the acute arthritis model.

Conclusion: Our data suggest that the transgenic mice model could be used to study transcriptional regulation of the IL-1beta gene expression in the inflammatory process and evaluation the effect of anti-inflammatory drug in vivo.