Neutrophil Kinetics in Systemic Inflammation

Marjolein Heeres

Promoter:
Prof.dr. L.P.H. (Loek) Leenen & Prof. dr. L. (Leo) Koenderman
Co-promoter:
Dr. K.J.P. (Karlijn) van Wessem
Date:
June 26, 2018
Time:
18:00 h

Summary

Upon severe systemic inflammation, evoked by e.g. trauma, sepsis and ischemia/reperfusion a systemic inflammatory response syndrome (SIRS) can be evoked. This inflammatory condition is characterized by activation of neutrophils and appearance of neutrophil subsets in the peripheral blood. An aberrant response can lead to inflammatory complications with detrimental consequences for the host. Until now it is not known which patients are prone to develop inflammatory complications. And also attempts to dampen the immune response with the use of immunomodulating drugs has not yet proven to successful.
In the first part of this thesis neutrophils kinetics during systemic inflammation evoked by polytrauma, hypothermia and endotoxemia (LPS challenge) were studied. Three subsets of neutrophils have been identified and kinetics are described during several DAMP and PAMP induced inflammatory responses. 
In the second part of this thesis a potential immunosuppressive drug, C1-esterase inhibitor (C1-INH), has been tested in order to attenuate the excessive immune response both in a LPS challenge model and in polytrauma patients. In both studies there was a lack of effect of C1-INH on the neutrophil kinetics.
Taken together, this thesis describes the neutrophil kinetics during systemic inflammation in detail and this can possibly help interpreting and predicting the appearance of systemic inflammatory complications after trauma.