Validation of Imiquimod- and LPS-induced Skin Inflammation Models and Their Application in the Investigation of Azithromycin Concentration in Inflamed, Infected, and Healthy Subcutaneous Tissue

This single-center, prospective, open-label, adaptive, pharmacokinetic study will comprise three parts: Part 0a-c, Part A, and Part B.

Objectives: This study primarily aims to characterize and establish a new skin inflammation model using topically applied LPS. The secondary aim of this research is to deepen our understanding of the role of leukocytes as potential transport vehicles for macrolides and other antibiotics in humans.

Intervention: Part 0 will serve as a pilot experiment in healthy volunteers to validate the imiquimod and LPS challenge in a controlled design. The investigators will clinically assess the tolerability of increasing LPS doses and the already published design of the imiquimod challenge. In general, the investigators will perform the different designs of skin inflammation models using tape stripping and an occlusive 18-mm Finn chamber.

The inflammation will not only be clinically assessed but also objectively quantified using the imaging-based mobile phone application Scarletred®Vision. Considering these results, the investigators will again carry out the LPS and imiquimod challenge in healthy volunteers and additionally perform biopsies in Part 0c to collect specimens for flow cytometry. Thus, the investigators will be able to characterize the skin inflammation models at a cellular level. Using NGS, the investigators will also explore transcriptional changes within cell subset that are affected by the inflammation.

In Part 0c, the investigators will include 12 healthy volunteers and will perform in each subject three skin punch biopsies, including a negative control, IMQ-challenged skin and LPS-challenged skin. Using flow cytometry, the investigators will measure the infiltration of leukocytes subsets.