Complement-related sterile inflammation

Topic leader:
Pischke, Søren

Description

Sterile inflammation is dependent on Complement System and Toll-like receptor activation. We aim to attenuate this inflammation by therapeutic inhibition.

Ischemia/reperfusion (I/R) injury is a key challenge in a number of widespread diseases like heart infarction, circulatory arrest, traumatic injury, and organ transplantation. These conditions have different etiologies, but the underlying mechanism is the same, i.e. cell death due to stop of blood supply during ischemia and aggravation of organ damage after restoration of blood supply during reperfusion.

The projects within this topic aim to resolve this challenge by significantly reducing tissue injury in the course of I/R using a novel and groundbreaking therapy of double inhibition of the innate immune system, namely the complement system and the toll-like receptors (TLR).

Our group’s previous results in bacterial infection models indicate that double inhibition of the complement system and the TLRs is superior to single intervention targeted to either the complement system or the TLRs alone. However, this close relationship between the complement system and the TLRs is not as obvious in I/R injury.  Both, single inhibition of the complement system or specific single receptors of the TLRs during I/R have shown promising experimental results (latest demonstrated by the topic leader in a myocardial infarction pig model), while clinical studies have been negative or without results so far.

Projects

Transplantation

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Cardiac arrest and therapeutic hypothermia

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Mitochondrial DNA

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