The Complement System and the CD14/TLR4/MD2 Complex as Targets for Therapy in Sepsis, 2016

The aim of this project was to develop a new therapeutic regime in conditions where the congenital immune system is over-activated and causes serious disease, as seen by sepsis (blood poisoning). Previous studies showed that inhibition of two important branches of the immune system, the complement system and the TRL system, inhibits the activation triggered by bacteria and other foreign substances in the test tube. In particular, combined inhibition of these systems gives a good effect. In this project it was found that a substance called coversin (OmCI) effectively inhibits complement factor 5 in both pigs and human beings. Further, the study worked with an antibody targeting CD14, a central molecule in the TLR system, and compared this to other inhibitors of the TLR family, such as anti-MD2. It was found that inhibition of CD14 is particularly effective in inhibiting activation and that the combination of inhibiting complement and CD14 is particularly effective in sepsis in pigs. The latest work published in the project, revealed to a large degree why clinical trials conducted to treat blood poisoning with the inhibition of the innate immune system (TLR4 / MD2) have not worked. This worked was published in the 'Journal of Infectious Diseases'.