Netrin-1 dampens pulmonary inflammation during acute lung injury.

RATIONALE: Acute lung injury (ALI) is an inflammatory disorder characterized by hypoxemia and diffuse infiltration of neutrophils into the alveolar space. The migration and extravasation of neutrophils is guided through positive guidance cues, such as chemokines. Recent work has identified the neuronal guidance protein netrin-1 to be a negative guidance cue for leukocyte migration and to hold antiinflammatory potential. OBJECTIVES: To test the role of pulmonary netrin-1 during ALI. METHODS: Pulmonary netrin-1 expression was evaluated during acute inflammation in vitro and in vivo; the netrin-1 promoter was studied using pGL4 luciferase reporter. ALI was induced through LPS inhalation and mechanical ventilation in wild-type, Ntn1(+/-), and A2BAR(-/-) animals. Exogenous netrin-1 was used to evaluate its impact on pulmonary inflammation. MEASUREMENTS AND MAIN RESULTS: Wild-type animals demonstrated repression of pulmonary netrin-1 after LPS inhalation. In vitro studies confirmed the repression of netrin-1. Studies in the putative netrin-1 promoter identified a nuclear factor-kappaB-dependent mechanism to be involved in this repression. Ntn1(+/-) animals demonstrated increased inflammatory changes after LPS inhalation compared with Ntn1(+/+) animals. Reconstitution with netrin-1 dampened the infiltration of neutrophils and cytokine production in the alveolar space. This effect was dependent on the adenosine 2b receptor. The importance of netrin-1 for the control of pulmonary inflammation could be corroborated in a model of ventilator-induced lung injury. CONCLUSIONS: Pulmonary netrin-1 levels are repressed during ALI. This results in pronounced pulmonary damage, an increased infiltration of neutrophils, and increased pulmonary inflammation. Exogenous netrin-1 significantly dampens the extent of ALI through the adenosine 2B receptor.

[The intensive care in the German Diagnosis Related Groups-System]. / Die Intensivmedizin im deutschen DRG (Diagnosis Related Groups)-System.

The introduction of a prospective per case reimbursement system in the year 2004 in Germany put the high end intensive care medicine to a considerable financial risk on the basis of risk selection and high maintenance costs. To face this situation, the German Interdisciplinary Union for Intensive Care Medicine (DIVI) suggested to encode intensive care services as a DRG procedure and thus to make them relevant for reimbursement. That is the case now since 2007. The suggested procedure, called " complex intensive care treatment ", is based on a new intensive care scoring system ("Cost Predictor Score") which should quantify the costs per case. This paper provides an introduction into the GR-DRG (German Refined--Diagnosis Related Groups) health care reimbursement system and its financial implications for expensive hospital departments and presents a study carried out in the Anaesthesiological Intensive Care Unit of the Tübingen University Hospital examining the suitability of this new intensive care scoring system.