Inhalative IL-10 Attenuates Pulmonary Inflammation following Hemorrhagic Shock without Major Alterations of the Systemic Inflammatory Response

Several studies report immunomodulatory effects of endogenous IL-10 after trauma. The present study investigates the effect of inhalative IL-10 administration on systemic and pulmonary inflammation in hemorrhagic shock. Male C57/BL6 mice (8 animals per group) were subjected to pressure-controlled hemorrhagic shock for 1.5 hrs followed by resuscitation and inhalative administration of either 50 μL PBS (Shock group) or 50 μg/kg recombinant mouse IL-10 dissolved in 50 μL PBS (Shock + IL-10 group). Animals were sacrificed after 4.5 hrs of recovery and serum IL-6, IL-10, KC, and MCP-1 concentrations were measured with ELISA kits. Acute pulmonary inflammation was assessed by pulmonary myeloperoxidase (MPO) activity and pulmonary H&E histopathology. Inhalative IL-10 administration decreased pulmonary inflammation without altering the systemic concentrations of IL-6, IL-10, and KC. Serum MCP-1 levels were significantly reduced following inhalative IL-10 administration. These findings suggest that inhalative IL-10 administration may modulate the pulmonary microenvironment without major alterations of the systemic inflammatory response, thus minimizing the potential susceptibility to infection and sepsis

Sobre la presència de Teucrium pumilum i Teucrium libanitis (Lamiaceae) a la província de València.

12p. fotog.color.[EN] About the presence of Teucrium pumilum and Teucrium libanitis (Lamiaceae) in the Valencian province, Spain.- Teucrium pumilum and T. libanitis have been cited from Valencia province (Spain) since the middle of the XXth Century from the gypsic soils in the Valle de Ayora-Cofrentes shire. The analysis of specimens and labels is not conclusive; no specimen would certify the presence of any of these taxa. The field identification and their inclusion in a phyotosociological table (relevé) by Rivas Goday are the only basis of their presence in the territory in a particular moment of the recent Spanish botanical history. Additionally, the unique herbarium specimen from Valencia, impossible to assign a concrete geographic locality, which was traditionally assigned to T. pumilum by some authors, is actually its congeneric T. carolipaui.[ES] Sobre la presencia de Teucrium pumilum y Teucrium libanitis (Lamiaceae) en la provincia de Valencia.- Teucrium pumilum y T. libanitis son dos especies que han sido citadas como presentes en la provincia de Valencia desde mediados del siglo XX, para los yesos que afloran en la comarca del Valle de Ayora-Cofrentes. El análisis de las etiquetas de los pliegos de los herbarios no es concluyente; ningún pliego testigo certificaría la presencia de estas especies. La determinación de visu por parte de Rivas Goday, y su inclusión en una tabla de inventarios fitosociológica, son el único fundamento de su existencia en la zona en algún momento determinado de la reciente historia botánica española. Además, para T. pumilum, el pliego de herbario que tradicionalmente se ha asignado a la cita valenciana se trata de una confusión en la determinación por parte de algunos autores con su congénere T. carolipaui, siendo imposible al mismo tiempo asignar una localidad geográfica concreta a este material.[CAT] Sobre la presència de Teucrium pumilum i Teucrium libanitis (Lamiaceae) a la província de València.- Teucrium pumilum i T. libanitis són dues espècies que han estat citades com a presents a la província de València des de mitjans del segle XX, sobre els guixos que afloren a la comarca de la Vall d’Aiora-Cofrents. L’anàlisi de les etiquetes dels plecs dels herbaris no és concloent; cap plec testimoni certificaria la presència d’aquestes espècies. La determinació de visu per part de Rivas Goday, i la seva inclusió en una taula d’inventaris fitosociològica, són l’únic fonament de la seva existència a la zona en un moment determinat de la recent història botànica espanyola. A més, per a T. pumilum, el plec d’herbari que tradicionalment s’ ha assignat a la cita valenciana es tracta d’una confusió en la determinació per part d’alguns autors amb el seu congènere.Peer reviewe

Recurrent Recruitment Manoeuvres Improve Lung Mechanics and Minimize Lung Injury during Mechanical Ventilation of Healthy Mice

INTRODUCTION: Mechanical ventilation (MV) of mice is increasingly required in experimental studies, but the conditions that allow stable ventilation of mice over several hours have not yet been fully defined. In addition, most previous studies documented vital parameters and lung mechanics only incompletely. The aim of the present study was to establish experimental conditions that keep these parameters within their physiological range over a period of 6 h. For this purpose, we also examined the effects of frequent short recruitment manoeuvres (RM) in healthy mice. METHODS: Mice were ventilated at low tidal volume V(T) = 8 mL/kg or high tidal volume V(T) = 16 mL/kg and a positive end-expiratory pressure (PEEP) of 2 or 6 cm H(2)O. RM were performed every 5 min, 60 min or not at all. Lung mechanics were followed by the forced oscillation technique. Blood pressure (BP), electrocardiogram (ECG), heart frequency (HF), oxygen saturation and body temperature were monitored. Blood gases, neutrophil-recruitment, microvascular permeability and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) and blood serum as well as histopathology of the lung were examined. RESULTS: MV with repetitive RM every 5 min resulted in stable respiratory mechanics. Ventilation without RM worsened lung mechanics due to alveolar collapse, leading to impaired gas exchange. HF and BP were affected by anaesthesia, but not by ventilation. Microvascular permeability was highest in atelectatic lungs, whereas neutrophil-recruitment and structural changes were strongest in lungs ventilated with high tidal volume. The cytokines IL-6 and KC, but neither TNF nor IP-10, were elevated in the BAL and serum of all ventilated mice and were reduced by recurrent RM. Lung mechanics, oxygenation and pulmonary inflammation were improved by increased PEEP. CONCLUSIONS: Recurrent RM maintain lung mechanics in their physiological range during low tidal volume ventilation of healthy mice by preventing atelectasis and reduce the development of pulmonary inflammation

A mouse intensive care unit to study TNF-induced sepsis and acid-induced lung injury

Acute lung injury (ALI) is a life threatening heterogeneous lung disease caused by a variety of intra- and extra-pulmonary inflammatory insults, including ventilator-induced lung injury, sepsis and gastric aspiration. So far no curative therapy is available for patients suffering from ALI and its more severe form acute respiratory distress syndrome (ARDS), which have a mortality of approximately 40%. Animal models are indispensable to elucidate the pathomechanisms of ALI and to develop successful therapeutic strategies. Although mice are the most frequently used species in laboratory practice, their small size poses a challenge regarding the measurement of respiratory and cardiovascular parameters. As a result, mouse models giving comprehensive information on the mechanisms of ALI under consideration of the physiological consequences are largely lacking. The present thesis aimed to examine the pathomechanisms of ALI in different injury models under consideration of clinically relevant physiological parameters. Therefore, a mouse intensive care unit (ICU) was developed that facilitates non-injurious mechanical ventilation under permanent physiological monitoring resulting in stable pulmonary and cardiovascular functions. For this purpose the role of recruitment manoeuvres (RM) at low and moderately high levels of tidal volume (VT) (8 versus 16 mL/kg) and positive end-expiratory pressure (PEEP) (2 versus 6 cmH2O) was examined. The current study demonstrated that protective non-injurious ventilation of mice requires the application of recurrent short RM to avoid atelectasis and further confirmed a protective effect of low VT and an increased PEEP level. Stable cardiovascular functions were achieved by intra-arterial volume substitution, regulation of body temperature and adequate anaesthesia. This setup provided all necessary parameters to determine experimental ALI, including oxygenation, pulmonary inflammation, oedema formation and histopathology, and is therefore useful for studies on ALI. A further objective was to examine the effect of a lethal systemic dose tumour necrosis factor (TNF) on the lungs of wild-type and acid sphingomyelinase-deficient (ASM-/-) mice. The pro-inflammatory cytokine TNF and the ceramide-generating enzyme ASM both play an important role in the pathogenesis sepsis, which is the main cause for extra-pulmonary ALI. The mouse ICU with its life supporting features facilitated to conduct this study. Despite of the supportive strategies, TNF caused septic shock, which was lethal in a significant number of wt mice. Of note, ASM-/- mice were protected from the cardiovascular depression and mortality, validating a pivotal role of ASM in sepsis. Somewhat surprisingly, TNF-induced sepsis did not cause lung injury. Finally, a model was required that causes a reproducible lung injury and allows the investigation of the effectiveness of therapeutic drugs in ALI, in particular the usefulness of steroids, which is currently under debate. For this purpose the model of acid-induced lung injury was chosen, because it resembles important clinical features of intra-pulmonary ALI. Instillation of acid with pH 1.5 caused inflammation and profound structural changes in the lung, leading to a loss of lung functions and severe hypoxemia. Treatment with the glucocorticoid dexamethasone proved to be anti-inflammatory, but did not prevent physiological dysfunction. In contrast, acid with pH 1.8 induced moderate lung injury with mild hypoxemia and predominantly inflammatory processes that were susceptible to dexamethasone. For the first time it was shown in an animal model of intra-pulmonary lung injury that steroid treatment significantly improved not only neutrophil recruitment and oedema formation, but also lung functions and oxygenation. A further therapeutic approach with the anti-inflammatory drug quinine failed to improve lung injury. In conclusion, the mouse ICU established here allows non-injurious ventilation under monitoring of clinically relevant parameters, provides life supporting measures, as shown in the TNF model, and is useful to conduct injury models. A final cluster analysis revealed three patterns of ALI: a ‘classical’ inflammation-dependent pathway and two injury mechanisms that are not related to inflammation, namely low-volume injury and chemical damage. These results suggest that the clinical effectiveness of anti-inflammatory drugs, such as steroids, may depend on the aetiology of ALI