Project Details
Projekt
Interactions between local and systemic immune response following controlled cortical impact injury in a rat model
Applicant
Professor Dr. Ulrich Thomale
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
from 2003 to 2011
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5407565
Innate immune response following major injury is a well-known phenomenon, and correlations between trauma severity, cytokine plasma levels and development of infectious complications are reported. In this scenario brain injury was found to be an independent risk factor for infectious complications in polytrauma patients. In previous studies we found that early posttraumatic IL-6 plasma levels are predictive for the outcome of brain injury regarding pneumonia, ventilation time, and lethality. The mechanisms of this relation are poorly understood. In experimental studies we demonstrated that local delivery of IL-1b into the brain induces a switch of the systemic immune responsiveness by decreasing the secretion of pro-inflammatory (e.g. TNF-a) and increasing the release of anti-inflammatory cytokines (e.g. IL-10) through activation of the hypothalmic pituitary adrenal (HPA)-axis and the sympathetic nervous system (SNS). With this background our hypothesis is that brain injury leading to the local secretion of pro-inflammatory cytokines like IL-1b, IL-6, TNF-a, produces a local pro-inflammatory but systemic anti-inflammatory response syndrome. The latter is characterized by increased IL-10 but diminished TNF secretion and APC activity of peripheral monocytes/macrophages. The systemic IL-6 release is either result of transpassing brain-derived IL-6 into circulation or stress-mediator induced peripheral IL-6 release. The resulting scenario seems to be a systemic immunodepression which is associated with an increased risk to develop infections. The severity of the local and systemic immune response may depend on the severity of the brain injury. The aim of the present study is, therefore, to investigate the local and systemic immune response following a cortical impact injury in a rat model depending on the severity of the trauma by functional assays and molecular biology studies. This model corresponds to a cortical contusion in humans. Furthermore, the effect of an additional major trauma (e.g. hemorrhage) has to be elucidated.
DFG Programme
Priority Programmes
Participating Persons
Professor Dr. Hans-Dieter Volk; Professor Dr. Christian Woiciechowsky
