Non-invasive bioluminescence imaging as a standardized assessment measure in mouse models of dermal inflammation

Abstract

Background: Myeloperoxidase is used as a marker and diagnostic tool for inflammatory processes. Hypochlorous acid produced by myeloperoxidase oxidizes luminol to produce light. By injecting luminol into experimental animals, inflammatory processes can be tracked in real-time by bioluminescence imaging (BLI).

Objective: We aimed to establish BLI as a standardized assessment measure in three mouse models of dermal inflammation.

Methods: Oxazolone-induced delayed-type-hypersensitivity (DTH) (acute), a model for dermatitis, imiquimod (IMQ) (sub-chronic) model for psoriasis and the (chronic) bleomycin model for scleroderma were used. In the first two models, dexamethasone and clobetasol, respectively, were used as reference compounds. In all cases, classical readouts such as dermal swelling, severity scores and histological analyses were compared with in- vivo bioluminescence.

Results: In DTH, bioluminescence peaked earlier than ear swelling, reflecting early cell infiltration. Dexamethasone blocked both ear swelling and bioluminescence. In the IMQ model, bioluminescence closely reflected the psoriasis scores and histology and revealed a relapse-remitting course of the disease. Clobetasol partially decreased the disease severity. After stopping IMQ and clobetasol treatment, BLI adopted a rhythmic pattern during resolution. Bleomycin induced an increase in bioluminescence and in collagen thickness. BLI revealed a time-course of the effects of bleomycin that was not reflected by histology alone.

Conclusion: For drug discovery and translational purposes, it is important that disease processes be tracked in vivo and possibly over a long period. We conclude that BLI is a valuable and reliable method for in-vivo measurement of dermal inflammation and potentially for inflammation resolution.

Keywords: Bioluminescence imaging; Bleomycin; Delayed-type-hypersensitivity; Imiquimod; Luminol.