Abstract
The treatment of inflammatory bowel disease (IBD) is still challenging. Therefore, it is crucial not only to develop new drugs specifically targeting IBD but also to evaluate the application and efficacy of already established pharmaceuticals used for related disorders. A promising new candidate is Voclosporin (Voc), a recently approved drug for lupus nephritis. In this study, we aimed to further elucidate the efficiency and the molecular mechanism of action of Voclosporin in comparison with its analogon cyclosporine A (CsA). Using an experimental colitis model and human PBMCs, we performed a comprehensive analysis including mini-endoscopy, histopathology, multi-photon endomicroscopy (MPEM), immunofluorescence staining, flow cytometry, and cytokine secretion profiling of murine lamina propria mononuclear cells (LPMCs). Treatment with Voc or CsA improved colitis-associated weight loss and reduced intestinal inflammation as assessed by endoscopy and histopathological stainings. Treatment with Voclosporin led to a significant increase of the barrier-strengthening protein claudin 3 in the colon of mice with experimentally induced colitis. Furthermore, treatment of stimulated human-derived PBMCs from healthy controls with Voclosporin and CsA inhibited the activation of IL2-inducible tyrosine kinase ITK, a known trigger of inflammation in IBD. These results further support the potential of Voclosporin as a promising therapeutic strategy for the treatment of acute intestinal inflammation.