Dexamethasone attenuates VEGF expression and inflammation but not barrier dysfunction in a murine model of ventilator-induced lung injury.

Background: Ventilator-induced lung injury (VILI) is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF) has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar-capillary barrier dysfunction in an established murine model of VILI.

Effect of interferon-β on neuroinflammation, brain injury and neurological outcome after experimental subarachnoid hemorrhage.

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) has a poor outcome, particularly attributed to progressive injury after the initial incident. Several studies suggest a critical role for inflammation in lesion progression after SAH. Our goal was to test whether treatment with anti-inflammatory interferon-β, which has shown promise as a therapeutic agent in experimental ischaemic stroke, can protect the brain after SAH.

Liposome-encapsulated dexamethasone attenuates ventilator-induced lung inflammation.

Background And Purpose: Systemic glucocorticoid therapy may effectively attenuate lung inflammation but also induce severe side-effects. Delivery of glucocorticoids by liposomes could therefore be beneficial. We investigated if liposome-encapsulated dexamethasone inhibited ventilator-induced lung inflammation.

Angiopoietin-1 treatment reduces inflammation but does not prevent ventilator-induced lung injury.

Background: Loss of integrity of the epithelial and endothelial barriers is thought to be a prominent feature of ventilator-induced lung injury (VILI). Based on its function in vascular integrity, we hypothesize that the angiopoietin (Ang)-Tie2 system plays a role in the development of VILI. The present study was designed to examine the effects of mechanical ventilation on the Ang-Tie2 system in lung tissue.

Interferon-β attenuates lung inflammation following experimental subarachnoid hemorrhage.

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) affects relatively young people and carries a poor prognosis with a case fatality rate of 35%. One of the major systemic complications associated with SAH is acute lung injury (ALI) which occurs in up to one-third of the patients and is associated with poor outcome. ALI in SAH may be predisposed by neurogenic pulmonary edema (NPE) and inflammatory mediators.

Ventilator-induced endothelial activation and inflammation in the lung and distal organs.

Introduction: Results from clinical studies have provided evidence for the importance of leukocyte-endothelial interactions in the pathogenesis of pulmonary diseases such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), as well as in systemic events like sepsis and multiple organ failure (MOF). The present study was designed to investigate whether alveolar stretch due to mechanical ventilation (MV) may evoke endothelial activation and inflammation in healthy mice, not only in the lung but also in organs distal to the lung.

Methods: Healthy male C3H/HeN mice were anesthetized, tracheotomized and mechanically ventilated for either 1, 2 or 4 hours.

Exogenous surfactant attenuation of ischemia-reperfusion injury in the lung through alteration of inflammatory and apoptotic factors.

Objective: Lung ischemia-reperfusion injury is associated with impaired gas exchange from increased edema formation and surfactant inactivation. Surfactant replacement therapy is believed to improve gas exchange and lung function, but its effect on inflammation is less well understood. We therefore examined the effects of exogenous surfactant on inflammatory and apoptotic factors in the lung in a rat model of lung ischemia-reperfusion injury.

Inflammatory consequences of lung ischemia-reperfusion injury and low-pressure ventilation.

Background: Lung ischemia-reperfusion injury (LIRI) is a clinical problem observed during thoracic surgery, and adversely affects patient recovery. A better understanding of the mechanisms of LIRI could be helpful to develop new therapeutic strategies. The objective was to assess the inflammatory and apoptotic consequences of LIRI using an in vivo rat model.

Stress-related peripheral neuroendocrine-immune interactions in women with ulcerative colitis.

Objectives: The mechanisms underlying the interaction of psychological stress with the disease course in inflammatory bowel diseases remain unclear. We analyzed the neuroendocrine and cellular immune responses to public speaking stress, and the in vitro adrenergic and glucocorticoid modulation of cytokine production by peripheral blood cells (PBCs) in women with ulcerative colitis (UC) compared to healthy female controls.

Methods: In 22 female UC patients with inactive disease or mild disease activity and 24 healthy females we analyzed the neuroendocrine and cellular immune responses to public speaking stress and the vitro beta-adrenergic and glucocorticoid regulation of IL-10 and TNF-alpha production by PBCs.

Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission.

Objective: Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases.

Methods: We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15).

Hydrogen peroxide impairs GRK2 translation via a calpain-dependent and cdk1-mediated pathway.

Oxidative mechanisms of injury are involved in many neurodegenerative diseases such as stroke, ischemia-reperfusion injury and multiple sclerosis. G protein-coupled receptor kinase 2 (GRK2) plays a key role in G protein-coupled receptor (GPCR) signaling modulation, and its expression levels are decreased after brain hypoxia/ischemia and reperfusion as well as in several inflammatory conditions. We report here that hydrogen peroxide downregulates GRK2 expression in C6 rat glioma cells.

Changes in innate and acquired immune responses in mice with targeted deletion of the dopamine transporter gene.

The dopamine transporter (DAT) is responsible for the re-uptake of dopamine into presynaptic nerve terminals and thereby controls dopaminergic neurotransmission. Deletion of DAT results in a hyperdopaminergic phenotype and DAT(-/-) mice are characterized by pituitary hypoplasia, impaired maternal behavior, and increased locomotion. From earlier studies, we have evidence that the activity of the central dopaminergic system may play a role in determining immune reactivity and disease susceptibility.

Tissue specific effects of the beta 2-adrenergic agonist salbutamol on LPS-induced IFN-gamma, IL-10 and TGF-beta responses in vivo.

Beta2-adrenergic agonists have immunomodulatory effects both in vitro and in vivo. We describe that oral salbutamol (beta-adrenergic agonist) administration has tissue-specific effects on cytokine production induced by intraperitoneal (i.p.

Reduced GRK2 level in T cells potentiates chemotaxis and signaling in response to CCL4.

Chemokine receptors belong to the family of G-protein-coupled receptors (GPCR). Phosphorylation of GPCR by GPCR kinases (GRKs) is considered to play an important role in desensitization of these receptors. We have recently shown in patients with rheumatoid arthritis that the level of GRK2 in lymphocytes is reduced by approximately 50%.

High and low responders to novelty and mesolimbic noradrenaline: effects of noradrenergic agents on radial-maze performance.

The authors used high and low responders to novelty (HRs and LRs, respectively) to examine the effects of noradrenergic injections into the nucleus accumbens using a special radial-maze task. During the 5 successive test days, solvent-treated HRs acquired this task faster than LRs. Isoproterenol (beta-agonist) combined with phenylephrine (alpha-agonist) improved acquisition in LRs but not in HRs; this effect was counteracted by propranolol (beta-antagonist) and phentolamine (alpha-antagonist).

The beta 2-adrenergic agonist salbutamol potentiates oral induction of tolerance, suppressing adjuvant arthritis and antigen-specific immunity.

Therapeutic protocols for treating autoimmune diseases by feeding autoantigens during the disease process have not been very successful to date. In vitro it has been shown that beta-adrenergic agonists inhibit pro-inflammatory cytokine production and up-regulate anti-inflammatory cytokine production. We hypothesized that the protective effect of oral administration of Ag would be enhanced by oral coadministration of the beta(2)-adrenergic agonist salbutamol.

Dynamics of mycobacterial HSP65-induced T-cell cytokine expression during oral tolerance induction in adjuvant arthritis.

Objective: To investigate whether oral administration of mycobacterial heat-shock protein 65 (HSP65) during adjuvant arthritis (AA) induces regulatory cells and cytokines.

Methods: AA was induced in Lewis rats and from the time of disease onset HSP65 in the presence of soya bean trypsin inhibitor (STI) was administered orally every other day. The number of splenic CD4+CD25+ T cells and antigen-induced cytokine mRNA expression were determined.

Adjuvant arthritis induces down-regulation of G protein-coupled receptor kinases in the immune system.

G protein-coupled receptors (GPCR) play a crucial role in the regulation of the immune response by, e.g., chemokines, PGs, and beta(2)-adrenergic agonists.

Treatment of adjuvant-induced arthritis by oral administration of mycobacterial Hsp65 during disease.

Objective: Oral administration of antigen prior to disease induction has been shown to induce peripheral tolerance in several experimental autoimmune diseases. However, the clinical benefit of pretreatment with antigens is limited. The aim of this study was to investigate whether adjuvant-induced arthritis (AIA) could be treated by oral administration of mycobacterial heat-shock protein 65 (Hsp65) during ongoing disease.

Oral antibiotics as a novel therapy for arthritis: evidence for a beneficial effect of intestinal Escherichia coli.

Objective: The intestinal flora is thought to play an important role in regulation of immune responses. We investigated the effects of changing the intestinal flora on the course of adjuvant-induced arthritis (AIA) and on experimental autoimmune encephalomyelitis (EAE) by the use of oral antibiotics.

Methods: Oral treatment with either vancomycin or vancomycin, tobramycin, and colistin was started after AIA and EAE induction.

Neonatal dexamethasone treatment increases susceptibility to experimental autoimmune disease in adult rats.

Major concern has emerged about the possible long term adverse effects of glucocorticoid treatment, which is frequently used for the prevention of chronic lung disease in preterm infants. Here we show that neonatal glucocorticoid treatment of rats increases the severity (p< or = 0.01) and incidence (p< or =0.