PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Systemic inflammation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed2004

The nexus between systemic inflammation and disordered coagulation in sepsis.

The innate immune system is designed as an early defense system that recognizes and clears potential microbial invaders. The coagulation system co-evolved with the innate immune system from a common ancestral cellular origin, and these two systems continue to exhibit a remarkable degree of integration in their signaling pathways and regulatory circuits following tissue injury and microbial invasion. Inflammatory mediators generate procoagulant signals and intravascular thrombosis activates multiple components of the innate immune system. The success of recombinant human activated protein C for the treatment of human septic shock is likely attributable to its combined effects as an endogenous anticoagulant and an anti-inflammatory molecule. Further advances in the management of severe infections may accrue with a better understanding of the integral link between coagulation and innate immunity.

Blood Coagulation Disorders↗
PubMed1997

Regulation of brain-derived T cells during acute central nervous system inflammation.

The unique immunologic environment of the central nervous system (CNS) regulates most local inflammatory responses. In some circumstances, however, immune-mediated injury to the brain can occur. To understand how lymphocytes are regulated within the CNS during an inflammatory response that does not produce immunopathology, we have studied T cells isolated from the brains of mice with Sindbis virus (SV) encephalitis. Even though they express activation markers, these T cells are arrested in the cell cycle and do not proliferate in vitro. Altered phosphorylation of the retinoblastoma gene product, a critical cell cycle regulator, appears to mediate this effect. Furthermore, while brain-derived T cells generate IFN-gamma, IL-4, and IL-10, these T cells are deficient in IL-2 production compared with peripheral T cells. This pattern of cytokine production occurs in cells that do not activate NF-kappaB normally. When T cells producing both IL-2 and IFN-gamma are adoptively transferred into SV-infected mice, some of these cells traffic into the brain. Those that enter the brain selectively down-regulate IL-2 production over time. Since normal brain lipids can inhibit IL-2 production and T cell proliferation in vitro, these substances may mediate these same effects in vivo. Collectively, these data show that the local environment of the CNS during SV encephalitis exerts a complex regulatory effect on T cells that are recruited into the brain. We speculate that this effect serves to prevent excessive local T cell reactivity. Whether and how this regulation might fail in the setting of autoimmune neurologic disease remains to be explored.

Acute Disease↗
PubMed2003

[Inflammation markers and risk stratification in patients with acute coronary syndromes: design of the SIESTA Study (Systemic Inflammation Evaluation in Patients with non-ST segment elevation Acute coronary syndromes)].

BACKGROUND AND OBJECTIVE: Evidence is growing regarding the prognostic value of markers of inflammation in unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). However, the independent value of these variables has not been systematically investigated in prospective studies. The main objective of the SIESTA study is to assess the relative prognostic roles of C-reactive protein, fibrinogen, neopterin, interleukins 6, 8, 10 and 18, tumor necrosis factor, e-selectin, endothelin 1, tissue factor, VCAM-1, ICAM-1, pregnancy-associated plasma protein-A, B-type natriuretic peptide, leukocytes, troponin I or T and serum creatine kinase-MB (CKMB) in UA/NSTEMI patients. PATIENTS AND METHOD: SIESTA is a prospective, multicenter trial involving patients with chest pain suggestive of acute coronary syndrome (ACS) within 48 hours of enrolment and at least one of the following: abnormal troponin levels, electrocardiographic signs of ischaemia or previously documented vascular disease. Clinical outcome data and serial biochemical determinations will be assessed during hospital admission and at 30, 180 and 365 days of follow-up. The TIMI (Thrombolysis In Myocardial Infarction) and PEPA (Proyecto de Estudio del Pronóstico de la Angina) risk scores will be also validated. Study variables will include death due to any cause, cardiac death, non-fatal myocardial infarction, unstable angina requiring re-admission, emergency revascularization and a composite of death, myocardial infarction and need for emergency hospitalization or myocardial revascularization. Each of these conditions will be treated as secondary end-points when assessed individually. This study will provide valuable prospective information about the prognostic value of inflammatory markers in real life ACS patients of Mediterranean origin.

Biomarkers↗
PubMed2005

Involvement of Disabled-2 protein in the central nervous system inflammation following experimental cryoinjury of rat brains.

Disabled-2 (Dab-2) functions in the mitogenic signal transduction pathway, and is expressed in a variety of tissues. We investigated the roles of Dab-2 expression in the rat brain following experimental cryoinjury in relation to central nervous system (CNS) inflammation. Western blot analysis showed that Dab-2 expression increased significantly (p < 0.001) in the frontal cortex 4-14 days after cryoinjury, and declined slightly thereafter. Immunohistochemistry showed that Dab-2 immunostaining occurred in most of the vessels in the control cerebral cortex. After cryoinjury, Dab-2 was localized in the majority of inflammatory cells (especially in ED1-positive macrophages) in the core and periphery, as well as in vessels. These findings suggest that Dab-2 is involved in the inflammation that follows CNS injury through the migration of activated inflammatory cells in the rat brain.

Adaptor Proteins, Vesicular Transport↗
PubMed2004

Thermal homeostasis in systemic inflammation: modulation of neuronal mechanisms.

Fever can be defined as a specific model of body temperature control, modified by action of humoral substances released due to bacterial infection. Under laboratory conditions exogenous and endogenous pyrogens affect nervous endings in the body periphery, as well as thermosensitive neurons in the hypothalamus, which first manifests as a shock reaction and then as shifts of temperature thresholds for activation of thermoregulatory effectors (cold thermogenesis, vasomotion, sweating or panting) to higher body temperatures. During the later phase of fever, the temperature threshold for cold thermogenesis starts to move downwards, while the thresholds for other thermoregulatory outputs remain elevated, the result being enlarging of the interthreshold zone. This creates conditions for cooling of the body and for termination of the fever. During different phases of fever cytokines, prostaglandins, neuropeptides and catecholamines participate in modulation of mechanisms regulating thermoregulatory functions. This paper aims to specify the role of individual cytokines in induction of fever, as well as in activation of thermoregulatory centers as well as individual thermoregulatory effectors and to define differences in their mode of action. The paper further attempts to summarize our knowledge on humoral modulation of the cytokine release. It is concluded that cytokines are not the primary factors responsible for setting of the body thermostat during fever.

Analgesics, Non-Narcotic↗
PubMed2003

Secondary lymphoid organ chemokines are elevated in the cerebrospinal fluid during central nervous system inflammation.

Secondary lymphoid organ chemokines have been implicated in chronic inflammation. Their expression in the central nervous system (CNS) has not been studied. Here, levels of secondary lymphoid organ chemokines CCL19 (Exodus-3, MIP-3beta), CCL21 (Exodus-2, 6Ckine, SLC) and CXCL12 (SDF-1alpha) were analysed by ELISA in cerebrospinal fluid (CSF) and plasma from patients with multiple sclerosis (MS); acute optic neuritis (ON) with oligoclonal IgG in the CSF (i.e., first bout of MS); acute ON without oligoclonal IgG (non-MS-type ON); other inflammatory neurological diseases (OIND); and non-inflammatory neurological diseases (NIND). NIND CSF contained CCL19 and CXCL12, while CCL21 was not detected. Intrathecal production of CCL19 and CCL21 was elevated in MS, MS-type ON, and OIND, but not in non-MS-type ON. In MS, CSF levels of CCL19 weakly correlated with CSF cell counts. Intrathecal production of CXCL12 was elevated only in OIND. The role of elevated CCL19 and CCL21 in MS could be retention of mature dendritic cells (DC) in the CNS, recruitment of nai;ve T cells and activated B cells, as well as de novo formation of secondary lymphoid structures in MS plaques.

Adult↗
PubMed2005

Ischemia/reperfusion: a clinically relevant model of intestinal injury yielding systemic inflammation.

BACKGROUND/PURPOSE: Multisystem organ failure (MSOF) is a major cause of morbidity and mortality in the critically ill patient. Animal models of endotoxin-induced sepsis were used to develop therapeutic regimens, which thus far have failed in clinical trials. Because multiple etiologies of MSOF affect the intestine, the authors hypothesized that during sepsis the gut may act as a possible trigger of the inflammatory cascade. As ischemia and reperfusion of the small intestine disrupts gut barrier function, thereby activating systemic inflammatory responses, the authors evaluated a murine model of ischemia/reperfusion to investigate these systemic responses to local mucosal and epithelial injury. METHODS: C57BL/10 and Balb/c mice underwent variable amounts of gut ischemia by superior mesenteric artery occlusion. Animals were evaluated for survival as well as gross and microscopic intestinal damage. RESULTS: Maximal ischemic damage occurred in the distal jejunum and proximal ileum. More severe epithelial damage and transmural inflammation were observed in C57BL/10 mice, which correlated with a higher mortality. CONCLUSIONS: This model mimics what is observed clinically with intestinal injury resulting from a progressive ischemic insult with eventual systemic manifestations. This reproducible model of systemic inflammation elicits variable responses from genetically different animals, the results of which may lead to a better understanding of MSOF.

Animals↗
PubMed2005

Influence of portal blood on the development of systemic inflammation associated with experimental acute pancreatitis.

BACKGROUND: The liver is a source of systemic proinflammatory mediators in acute pancreatitis. We have investigated the effects of blood from the pancreas and intestine in liver activation and lung inflammation during early stages of experimental acute pancreatitis in a rat model. METHODS: A portosystemic shunt and a mesosystemic shunt were created to prevent the passage of blood coming from the pancreas and the intestine, respectively, to the liver. Pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. After 3 hours, the inflammatory process in the lung and intestine, plasma levels of tumor necrosis factor (TNF)-alpha and their soluble receptor, and mRNA expression of inflammatory mediators in the lung were evaluated. RESULTS: Portocaval shunting of blood prevented the inflammatory process in the lung, an increase in plasma TNF-alpha concentration, and the expression of TNF-alpha, interleukin (IL)-1beta, and heat-shock protein (HSP)-72 in the lung, but had no effect on plasma levels of soluble TNF-alpha receptor or on expression of inducible nitric oxide synthase (iNOS) and macrophage inflammatory protein (MIP)-2 in the lung. In contrast, mesocaval shunting of blood did not modify any of the parameters evaluated. CONCLUSIONS: Pancreatic blood, but not intestinal blood, plays a key role in liver activation during experimental acute pancreatitis.

Acute Disease↗
PubMed2003

Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis.

A preestablished infection with the parasitic helminth, Schistosoma mansoni, significantly reduced the incidence and delayed the onset of experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice immunized with myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide. The altered disease progression was not solely due to the induction of a strong Th2 response, since intraperitoneal injection of schistosome eggs did not affect disease development. MOG-specific gamma interferon (IFN-gamma), nitric oxide, and tumor necrosis factor alpha production by splenocytes was significantly reduced in schistosome-infected mice compared to uninfected mice. However, similar levels of interleukin-10 (IL-10) were produced in an antigen-specific manner, suggesting that the induction of antigen-specific responses was not inhibited. Analysis of in vivo cytokine production by real-time PCR indicated that IL-12p40, but not IFN-gamma, transcript levels were dramatically reduced in the spinal cords of schistosome-infected, MOG-immunized mice. Furthermore, analysis of the cellular composition of the spinal cords and brains revealed that a preestablished infection with S. mansoni decreased central nervous system (CNS) inflammation, particularly of macrophages and CD4 T cells. These results suggest that schistosomiasis may negatively regulate the onset of EAE by downregulating the production of proinflammatory cytokines and altering CNS inflammation.

Animals↗
PubMed2003

Systemic inflammation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammation in the pulmonary tissue. The disease is associated with a switch from a self-limiting inflammatory response, mainly initiated by smoke inhalation, to a chronic persistent inflammatory response after prolonged interaction with cigarette smoke. The extent of the inflammatory reaction is correlated with the severity of the disease. Chronic inflammation in the pulmonary tissue is also associated with systemic effects. These effects range from cytokine-induced priming of peripheral leukocytes, to muscle wasting induced by cytokines such as tumour necrosis factor-alpha. Despite a general consensus that chronic inflammation is a characteristic phenomenon of the disease, surprisingly little is known regarding the underlying pathogenetic mechanisms. A clear communication is present between the disease mechanisms in the pulmonary compartment and peripheral tissues, leading to the concept of COPD as a systemic inflammatory disease. This communication can be mediated by: 1) leakage of reactive oxygen species and stress-induced cytokines directly into the peripheral blood, 2) (pre)activation of peripheral blood leukocytes that can result in aberrant homing and activation of inflammatory cells in distant tissues, and 3) the liberation of proinflammatory mediators by leukocytes and/or stromal cells present in the pulmonary tissues during progression of the disease. The current authors hypothesise that the occurrence of a chronic inflammatory response after prolonged interaction of the pulmonary tissue with cigarette smoke causes aberrant homing of leukocytes to the tissue and delayed apoptosis. This leads to the autonomous characteristic of the inflammatory response in patients with chronic obstructive pulmonary disease.

Humans↗
PubMed1997

Intrinsic fibrinolytic capacity and systemic inflammation: novel risk factors for arterial thrombotic disease.

Traditional risk factors, e.g. hyperlipidemia, cigarette consumption, blood pressure, family history, and diabetes, predict < 50% of all future cardiovascular events. This paper reviews the use of novel hemostatic and thrombotic markers, such as intrinsic fibrinolysis and systemic micro-inflammation, for the prediction of the risk of arterial thrombotic disease. It has been hypothesized that relative abnormalities in the hemostatic and thrombotic systems are common on a population basis, and that they predispose certain individuals to clinically pathologic thrombosis. Abnormal levels of fibrinolytic parameters have been shown to predict future cardiovascular events, and tissue-type plasminogen activator antigen appears to be the most useful of these markers. Low-grade chronic inflammation may play an important role in atherogenesis. Of the newer inflammatory parameters, C-reactive protein has been the best studied and evidence suggests that elevated levels of C-reactive protein can predict the future risk of both myocardial infarction and stroke, both in healthy individuals and in patients with known coronary artery disease. Results from clinical trials to evaluate whether modification of novel risk factors results in a net clinical benefit are limited at present. However, novel markers will probably provide new directions in both thrombosis research and disease prevention.

Arterial Occlusive Diseases↗
PubMed1994

Consequences of trauma: systemic inflammation and multiple organ dysfunction.

Critically injured patients are at risk for systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). MODS is a clinical syndrome of progressive physiologic dysfunction of organ systems. Trauma patients are at high risk for SIRS/MODS because of circulatory shock with tissue hypoxemia, tissue injury, and infection. Organ dysfunction may be a direct consequence of an insult (primary MODS) or may manifest latently (secondary MODS) and involves organs not initially injured. Management of SIRS/secondary MODS requires control/elimination of the source of inflammation, maintenance of tissue oxygenation, nutritional/metabolic support, support for individual organs, and effective pain control.

Humans↗
PubMed2002

Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care.

OBJECTIVE: Sepsis and systemic inflammatory response syndrome (SIRS) are major causes of morbidity and mortality after cardiopulmonary bypass. Attempts to suppress proinflammatory mediators have failed to improve outcomes in sepsis or in patients undergoing cardiopulmonary bypass. Recent work in adult patients has suggested that the balance between pro- and anti-inflammatory mediators is more important than the level of proinflammatory response alone. This balance may be reflected by the expression of monocyte human lymphocyte antigen (HLA)-DR, with low concentrations indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the relationship between monocyte HLA-DR expression and the subsequent development of sepsis/SIRS in children undergoing cardiopulmonary bypass. DESIGN: A prospective, observational, clinical study. SETTING: A tertiary pediatric cardiac center. PATIENTS: Eighty-two infants and children undergoing elective cardiac surgery between March and December 1999. MEASUREMENTS AND MAIN RESULTS: Monocyte HLA-DR expression was assessed before and after surgery and was found to be related to the length of hospital stay and the development of complications including sepsis/SIRS. The inflammatory insult of cardiopulmonary bypass decreased monocyte HLA-DR expression in all children. Lowest concentrations were seen within 72 hrs of surgery and were significantly lower in cases that subsequently required prolonged intensive care support (p <.0001, Mann-Whitney). HLA-DR expression on <60% of circulating monocytes was associated with a greatly increased risk of later (minimum 4 days) development of sepsis/SIRS (odds ratio, 12.9; 95% confidence interval, 3.4-47.5). Low HLA-DR was an independent predictor for the development of sepsis/SIRS after correction for age, bypass time, complexity of surgery, Paediatric Index of Mortality, and surgeon on multiple logistic regression analysis. CONCLUSIONS: Patients with decreased HLA-DR in the early postoperative period represent a subpopulation at greatly increased risk of later sepsis/SIRS. Such patients may benefit from strategies aimed to reduce this risk.

Adolescent↗
PubMed2005

The signal transduction pathways involved in hepatic cytochrome P450 regulation in the rat during a lipopolysaccharide-induced model of central nervous system inflammation.

It is well known that inflammatory and infectious conditions of the central nervous system (CNS) differentially regulate hepatic drug metabolism through changes in cytochrome P450 (P450); however, the pathways leading to this regulation remain unknown. We provide evidence delineating a signal transduction pathway for hepatic P450 gene expression down-regulation in an established rat model of CNS inflammation using lipopolysaccharide (LPS) injected (i.c.v.) directly into the lateral cerebral ventricle. Brain cytokine levels were elevated, and the expression of tumor necrosis factor alpha and inhibitor of kappaB alpha (IkappaBalpha) were increased in the liver following the i.c.v. administration of LPS, indicating the presence of an inflammatory response in the brain and liver. The expression of CYP2D1/5, CYP2B1/2, and CYP1A1 was down-regulated following CNS inflammation. The binding of several transcription factors [nuclear factor of the kappa enhancer in B cells (NF-kappaB), activator protein-1, cAMP response element binding protein, CCAAT-enhancer binding protein (C/EBP)] to responsive elements on P450 promoter regions was examined using electromobility shift assays. Binding of both NF-kappaB and C/EBP to the promoter regions of CYP2D5 and CYP2B1, respectively, was increased, indicating that they play an important role in the regulation of these two isoforms during inflammatory responses. Evidence is also provided suggesting that the rapid transfer of LPS from the CNS into the periphery likely accounts for the down-regulation of P450s in the liver.

Animals↗
PubMed2006

Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented by aldose reductase inhibition.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome characterized by excessive production of inflammatory cytokines and cardiovascular collapse. Postreceptor signaling events that lead to stress responses and cytokine production are sensitive to redox changes and products of lipid peroxidation. METHODS AND RESULTS: We tested the hypothesis that inflammatory signaling and cytokine generation during sepsis depend on the activity of the enzyme aldose reductase, which catalyzes the reduction of lipid peroxidation-derived aldehydes and their glutathione conjugates. The results of the present study show that pharmacological inhibition of aldose reductase by sorbinil or knockdown of the enzyme by small interfering RNA prevents the activation of nuclear factor-kappaB and the release of tumor necrosis factor-alpha from lipopolysaccharide-stimulated RAW264.7 or H9c2 cells. Increases in serum and cardiac cytokines in response to lipopolysaccharide challenge were suppressed by inhibition of aldose reductase. Treatment with sorbinil blunted the activation of protein kinase C, c-Jun NH2-terminal kinase, and p38, as well as phosphorylation of interleukin receptor-associated kinase, IkappaB-alpha, IkappaB kinase complex-alpha/beta, and phospholipase-gamma1 and -beta1. These changes were associated with decreased myocardial nuclear factor-kappaB and activating protein-1 activity, prostaglandin E2 production, induction of cyclooxygenase 2, and inducible nitric oxide synthase. Sorbinil treatment also induced functional recovery in myocardial fractional shortening in vivo and preserved contractile function of isolated perfused hearts. Inhibition of aldose reductase increased survival in mice injected with lethal doses of lipopolysaccharide. CONCLUSIONS: The present demonstration that aldose reductase mediates endotoxin-induced inflammation and cardiomyopathy suggests that inhibition of this enzyme may be useful to attenuate maladaptive host responses and to treat acute cardiovascular dysfunction associated with endotoxic shock.

Aldehyde Reductase↗
PubMed2002

Chlamydia pneumoniae, systemic inflammation and the risk of venous thrombosis.

Inflammatory mediators are involved in activation of the coagulation system, and elevated plasma concentrations of IL-6 and IL-8 are associated with an increased risk of venous thrombosis. Using serologic and molecular biologic tests, we investigated in a case-control study on patients with recurrent venous thrombosis the association between Chlamydia (C) pneumoniae and venous thrombosis and we evaluated the relation between C. pneumoniae serology and the cytokines IL-6 and IL-8. The presence of C. pneumoniae antibody titers > or = 1:16 was not associated with an increased risk of venous thrombosis (odds ratio 0.8 95% CI, 0.4-1.7). Circulating C. pneumoniae-DNA was detected in only one patient and two control subjects. IgG antibody titers against C. pneumoniae were not correlated with the concentrations of IL-6 and IL-8. These results indicate that the inflammatory process shown in patients with venous thrombosis is not related to C. pneumoniae.

Adult↗