Controlled and uncontrolled inflammatory responses: mechanistic insights and implications for early-phase clinical research

Abstract

This thesis describes research ultimately aimed at advancing immunological clinical drug development. The thesis is divided into two sections. First, it mechanistically explores controlled vascular and inflammatory effects of experimental human challenge models used for informing early-phase clinical research with novel therapeutics. Furthermore, it evaluates regulatory considerations and the insights gained from uncontrolled inflammatory effects in clinical trials.