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Results for “Systemic inflammation”

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At least 271 records · Page 15Linked to original sources
PubMed1999

Brain-IL-1beta induces local inflammation but systemic anti-inflammatory response through stimulation of both hypothalamic-pituitary-adrenal axis and sympathetic nervous system.

It is well established that systemic inflammation induces a counter-regulatory anti-inflammatory response particularly resulting in deactivation of monocytes/macrophages. However, recently we demonstrated a systemic anti-inflammatory response without preceding signs of systemic inflammation in patients with brain injury/surgery and release of cytokines into the cerebrospinal fluid (CSF). In order to analyze the mechanisms and pathways of systemic immunodepression resulting from sterile cerebral inflammation we established an animal model using continuous intra-cerebroventricular (i.c.v.) or intra-hypothalamic (i.h.) infusion of rat recombinant (rr) tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta for 48 h. Controls received intra-venous (i.v.) cytokine administration. Interestingly, i.c.v. and i.h. infusion of IL-1beta but not TNF-alpha produced distinct signs of central nervous system (CNS) inflammation. Correspondingly, i.c.v. infusion of IL-1beta particularly diminished the TNF-alpha but increased the IL-10 concentration in whole blood cultures after endotoxin stimulation. All parameters normalized within 48 h after termination of the infusion. Blocking the hypothalamic-pituitary-adrenal (HPA) axis by hypophysectomy (HPX) led to complete recovery of the diminished TNF-alpha concentration and temporarily inhibited the IL-10 increase. Blocking the sympathetic nervous system (SNS) transmission by application of the beta2-adrenoreceptor antagonist propranolol not only inhibited the increase but further downregulated the endotoxin induced IL-10 concentration in the media of whole blood cell cultures, whereas the TNF-alpha decrease was only partially prevented. Interestingly, HPX and propranolol also diminished the cell invasion into the CSF. In summary, activation of both the HPA axis and the SNS plays an important role in systemic anti-inflammatory response resulting from cytokines in brain and cerebral inflammation.

Animals↗
PubMed2004

Chronic transcutaneous electrical stimulation of calf muscles improves functional capacity without inducing systemic inflammation in claudicants.

OBJECTIVES: To assess whether electrical stimulation of ischaemic calf muscles in claudicants causes a systemic inflammatory response and to evaluate effects of its chronic application on muscle function and walking ability. DESIGN: Prospective randomised controlled trial of calf muscle stimulation. MATERIALS AND METHODS: Stable claudicants were randomised to receive either active chronic low frequency (6 Hz) motor stimulation (n=15) or, as a control treatment, submotor transcutaneous electrical nerve (TENS) stimulation (n=15) of calf muscles in one leg, 3 x 20 min per day for four weeks. Leucocyte activation was quantified by changes in cell morphology, vascular permeability by urinary albumin:creatinine ratio (ACR), calf muscle function by isometric twitch contractions and walking ability by treadmill performance pre- and post-intervention. RESULTS: Acute active muscle stimulation activated leucocytes less (28% increase) than a standard treadmill test (81% increase) and did not increase ACR. Chronic calf muscle stimulation significantly increased pain-free walking distance by 35 m (95% CI 17, 52, P<0.001) and maximum walking distance by 39 m (95% CI 7, 70, P<0.05) while control treatment had no effect. Active stimulation prevented fatigue of calf muscles during isometric electrically evoked contractions by abolishing the slowing of relaxation that was responsible for loss of force. CONCLUSIONS: Chronic electrical muscle stimulation is an effective treatment for alleviating intermittent claudication which, by targeted activation of a small muscle mass, does not engender a significant systemic inflammatory response.

Aged↗
PubMed2002

Glucocorticoids and central nervous system inflammation.

Glucocorticoids (GCs) are well known for their anti-inflammatory and immunosuppressive properties in the periphery and are therefore widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, or transplant rejection. This led to the assumption that GCs are uniformly anti-inflammatory in the periphery and the central nervous system (CNS). As a consequence, GCs are also used in the treatment of CNS inflammation. There is abundant evidence that an inflammatory reaction is mounted within the CNS following trauma, stroke, infection, and seizure, which can augment the brain damage. However an increasing number of studies indicate that the concept of GCs being universally immunosuppressive might be oversimplified. This article provides a review of the current literature, showing that under certain circumstances GCs might fail to have anti-inflammatory effects and sometimes even enhance inflammation.

Central Nervous System Diseases↗
PubMed2004

[The organ effects of systemic inflammation response activated during open heart surgery and current treatment methods].

Multi-organ failure may occur due to activation of systemic inflammatory process with many other factors in open-heart procedures when cardiopulmonary bypass is used. Activation of systemic inflammatory process may cause postoperative complications. Surgical trauma, contact of blood with foreign surface, endotoxemia and ischemia-reperfusion injury are major factors that contribute to activation of inflammatory response. In this review we purposed to investigate the factors which contribute to the systemic inflammatory process, multiorgan dysfunction and the therapeutic modalities during open heart surgery.

Cardiac Surgical Procedures↗
PubMed1997

Effects of alpha-trinositol on systemic inflammation and renal function in ovine bacterial sepsis.

Neuronally secreted peptides are important mediators of hemodynamic changes in the systemic inflammatory response. The inositol derivative D-myo-inositol[1,2,6]triphosphate (alpha-trinositol) has been demonstrated to be a specific nonpeptide antagonist of vasoconstriction induced by neuropeptide Y. We induced sepsis by a 48 h continuous infusion of Pseudomonas aeruginosa (10(6) colony-forming unit/min intravenously [i.v.]) in 12 chronically instrumented, conscious sheep. After 24 h, the animals were randomized to receive either alpha-trinositol (i.v. bolus of 2 mg/kg, followed by a continuous infusion of 3.5 mg/kg/h) or the saline carrier. alpha-Trinositol increased the heart rate (108 +/- 4 to 152 +/- 9 beats per minute) and reduced the stroke volume index (65 +/- 5 to 49 +/- 2 mL/beat/m2) but did not change cardiac index. Left ventricular stroke work decreased significantly (80 +/- 9 to 58 +/- 7 g.m/m2). All blood flows except the infrarenal aortic flow were increased after 24 h, but treatment decreased only the flow to the hind limb region. Urine output and fractional sodium excretion significantly increased without osmotic diuretic effects after alpha-trinositol. In treated animals, we found significantly lower leukocyte counts in all organ tissues. We conclude that alpha-trinositol modulates the cardiac performance and the local inflammatory response in tissues, and improves the fluid balance in septic sheep.

Animals↗
PubMed1998

Procalcitonin as a marker of systemic inflammation after conventional or minimally invasive coronary artery bypass grafting.

Cardiac surgery using cardiopulmonary bypass (CPB) often induces a systemic inflammatory response syndrome (SIRS). The concept of minimally invasive direct coronary artery bypass (MIDCAB) eliminates cardiopulmonary bypass. We evaluated the perioperative time course of procalcitonin (PCT) to compare the inflammatory response due to these two different surgical procedures. 57 patients were studied: CABG with CPB (n = 30), MIDCAB without CPB (n = 27). The following data were measured preoperatively, after induction of anesthesia, after separation from CPB in the CABG group or after left internal mammary artery (LIMA)-to-left anterior descending artery (LAD) anastomosis in MIDCAB group, and every 3 hours for the first 42 hours in the ICU: PCT, C-reactive protein (CRP), body temperature, hemodynamic parameters, and the need for catecholamines. Leucocyte counts were measured daily. For statistical analyses the Friedmann, Wilcoxon, or Mann-Whitney U tests were used. PCT in the CABG group rose to a maximum of 2.0 ng/ml (median) at 15 hrs postoperatively. In the MIDCAB group maximal PCT concentration was 0.7ng/ml (median) (p < 0.05). CRP was elevated to 17.1 mg/dl in the CABG and 18.5mg/dl in the MIDCAB group (n.s.). The leucocyte counts were increased on day 2 in the CABG group (p < 0.05). In the CABG group about 25% of the patients needed noradrenaline, but in the MIDCAB group none (p < 0.05). Body temperature did not differ between both groups. The increase in PCT concentration was more pronounced after CABG, indicating a reduced inflammatory response after MIDCAB. CRP was increased after both procedures. PCT reflects the inflammatory response after cardiac bypass surgery with or without CPB.

Aged↗
PubMed2004

Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections.

The inflammatory response to chronic infections such as periodontitis may be central to the systemic implications of these diseases. This study examined the possible association between specific gene polymorphisms and the systemic inflammatory response in individuals suffering from severe generalized periodontitis. Ninety-four subjects with periodontitis were genotyped for polymorphisms in IL-1A (-889), IL-1B (-511, +3954), TNF-A (-308), IL-6 (-174) and TLR4 (-299, -399) genes. We found that the genotypes for IL-1A or IL-6 are associated with higher levels of serum IL-6 (P < 0.03) and serum CRP (P < 0.05), similarly the TNF-A genotype is associated with higher levels of serum IL-6 (P < 0.05) after correction for age, body mass index, gender, ethnicity and cigarette smoking. Systemic inflammatory responses are higher in severe periodontitis patients carrying rare alleles for functional inflammatory gene polymorphisms. These results suggest that cytokine genotypes are important determinants of the systemic inflammatory response in subjects with periodontitis. Genetic polymorphism therefore, may in part explain the reported association between periodontitis and systemic disease.

Base Sequence↗
PubMed2004

Heme oxygenase modulates hepatic leukocyte sequestration via changes in sinusoidal tone in systemic inflammation in mice.

Heme oxygenase (HO) modulates the accumulation of leukocytes within the liver during the early stages of a systemic inflammatory response syndrome (SIRS), but the anti-inflammatory mechanism(s) remain to be tested. The influence of HO on the adhesion molecule expression within the liver and on circulating leukocytes was assessed. In addition, the effect of HO and nitric oxide synthase (NOS) on the liver microcirculation was tested. Mice were subjected to 1 h bilateral hindlimb ischemia followed by 3 h of reperfusion, at which time blood samples and the liver were harvested and adhesion molecule expression determined (ICAM-1, CD49d and CD11b). Direct measures of sinusoidal diameter and estimates of volumetric blood flow were obtained using intravital microscopy. HO was specifically induced and inhibited by hemin and chromium mesoporphyrin (CrMP), respectively, whereas NOS was inhibited by N-nitro-L-arginine methyl ester (L-NAME). ICAM-1 expression was increased following hindlimb ischemia-reperfusion. Hemin caused only a modest, but significant decrease in ICAM-1 expression, whereas inhibition of HO had no effect. However, HO inhibition significantly reduced sinusoidal diameters and volumetric flow and such vessels were correlated with significantly increased numbers of stationary leukocytes. Inhibition of NOS had no effect on sinusoidal diameter or volumetric flow. In conclusion, the anti-inflammatory benefits afforded by HO activity within the liver appear to involve the control of sinusoidal diameter and volumetric blood flow rather than altered adhesion molecule expression during the early stages of SIRS.

Animals↗
PubMed2000

The effect of dopexamine on regional tissue oxygenation, systemic inflammation and amino acid exchange in major abdominal surgery.

BACKGROUND: Beta-adrenergic agents are frequently used to improve cardiac performance in surgical and intensive care patients. Beta-adrenergic agents have metabolic and anti-inflammatory effects in addition to their cardiovascular effects. Splanchnic metabolic activity increases in response to surgery and inflammation. Dopexamine is believed to favor blood flow distribution to the splanchnic region. METHODS: We investigated the effect of dopexamine, started before major abdominal surgery, on postoperative patterns of systemic and regional blood flow, metabolic response, and markers of inflammation. Twenty-one patients undergoing major abdominal surgery were studied. All patients were stabilized preoperatively to predefined hemodynamic endpoints with fluids. After preoperative measurement of systemic and splanchnic oxygen transport and splanchnic lactate, glutamine and alanine exchange and blood levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6), the patients were randomized to receive an infusion of dopexamine at 0.5 microg kg(-1) min(-1) (group 1) or 2.0 microg kg(-1) min(-1) (group 2) or placebo. Measurements were repeated at 6 h and 24 h after the end of the operation and the blood levels of cytokines also at 36 h postoperatively. RESULTS: Dopexamine evoked an increase in cardiac index preoperatively. Postoperatively, there was no difference between the groups in systemic and regional hemodynamics or oxygen transport: cardiac index, splanchnic blood flow and oxygen delivery increased similarly in each group. Accordingly, systemic oxygen extraction decreased. Glutamine, alanine and lactate exchange did not differ between the groups. The only metabolic change was an increased splanchnic uptake of alanine, which also was unaffected by dopexamine. There was no difference between the groups in TNF and IL-6 levels; TNF level did not change, while IL-6 level increased in response to surgery. CONCLUSIONS: Dopexamine, when added to a preoperative stabilization protocol with fluids, did not augment the postoperative hemodynamic response, and had no effect on postoperative metabolic and inflammatory responses.

Abdomen↗
PubMed2004

Systemic inflammation and disseminated intravascular coagulation in early stage of ALI and ARDS: role of neutrophil and endothelial activation.

To determine the existence of a close link between inflammation and coagulation in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and to examine their prognostic value in the development of ARDS and clinical outcome, we made a prospective cohort study. The study subjects consisted of 57 patients: 19 patients with ARDS and 38 patients with ALI as defined by a Lung Injury Score of > or =2.5 and 1.0 to less than 2.5, respectively. According to the outcome, the patients were subdivided into the survivors and the nonsurvivors. Ten normal healthy volunteers served as control subjects. Plasma levels of soluble L-, P-, and E-selectins, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (sTM), and neutrophil elastase were measured within 24 h after the diagnosis of ALI or ARDS. The number of systemic inflammatory response syndrome (SIRS) criteria being met by the patients and the disseminated intravascular coagulation (DIC) scores were determined simultaneously. The number of SIRS criteria and the DIC scores of the patients with ALI or ARDS showed high values, and more than half of the patients were complicated by DIC. The levels of sL-selectin in both groups of the patients were significantly lower than those of the control subjects. All other soluble adhesion molecules, neutrophil elastase, and sTM in the patients with ALI and ARDS were markedly elevated than those in the control subjects. The levels sICAM-1, sVCAM-1, and sTM in the ARDS patients significantly increased compared with the ALI patients. The number of SIRS criteria and the DIC scores in the nonsurvivors showed higher values than those in the survivors. In addition, we found significant differences in the levels of soluble adhesion molecules, neutrophil elastase, and sTM between the survivors and the nonsurvivors. In conclusion, we found a concurrent activation of both inflammation and coagulation in the patients with ALI or ARDS. The results also suggest that systemic activation of inflammation and coagulation associated with endothelial injury has prognostic value for the development of ARDS and poor outcome.

Disseminated Intravascular Coagulation↗
PubMed2002

Macrophages and nitric oxide as the possible cellular and molecular basis for strain and gender differences in susceptibility to autoimmune central nervous system inflammation.

PVG rats are resistant to actively induced experimental autoimmune encephalomyelitis (EAE) and this appears to be directly related to high and sustained systemic levels of reactive nitrogen intermediates(RNI) following sensitization for EAE when compared to the highly susceptible Lewis rat. An apparent cellular basis for the different EAE susceptibility between the two rat strains is described. Spleens of PVG rats have increased monocyte/macrophage numbers(NO producing cells) and lower erythrocyte (NO scavengers) to nucleated spleen cell ratios compared with Lewis rats. Splenectomy demonstrated the pivotal role of the spleen in resistance to EAE as splenectomized PVG rats were rendered completely susceptible to disease induction. It was further demonstrated that EAE resistance in PVG rats is limited only to females and that only female PVG rats have increased splenic macrophage and an enhanced NO production following immunization. The males are fully susceptible to EAE and their spleen cell populations are similar to those of Lewis rats of either gender. Despite being resistant to active disease induction, immunized female PVG rats can generate EAE effector cells that are capable of passively transferring disease.Furthermore, female PVG rats are fully susceptible to passively transferred EAE. Thus, there appears to be no defect in the female PVG target tissue or in the processing or presentation of antigen,but a block at the level of effector cell expansion and/or recirculation and transmigration into the target tissue in actively induced EAE.

Animals↗
PubMed1999

Antibodies to CD44 and integrin alpha4, but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment.

The role of various adhesion molecules in lymphocyte homing to the brain and in inflammatory autoimmune disease of the central nervous system (CNS) was examined in mice. Activated T cell lines and clones expressed CD44 and integrin alpha4, but not L-selectin, and entered the CNS independent of their antigen specificity. mAbs directed against CD44 and integrin alpha4 prevented the transfer of experimental autoimmune encephalomyelitis (EAE) by myelin basic protein-specific T cells. T cells preincubated with anti-CD44 or antiintegrin alpha4 were blocked only partially from entering the brain parenchyma. However, both antibodies efficiently prevented CNS inflammation and clinical expression of EAE when injected in vivo. This effect lasted as long as antibodies were administered. Antibodies specific for L-selectin had no effect on homing of encephalitogenic T cells to the brain or development of EAE. Antiintegrin alpha4 and anti-CD44 did not impair the activation and function of encephalitogenic T cells in vitro and did not deplete integrin alpha4- or CD44-positive cells in vivo. These data suggest that, in the absence of leukocyte recruitment, the entry of a reduced number of activated myelin basic protein-reactive T cells in the CNS is not sufficient for the development and expression of EAE. We propose that antibodies to integrin alpha4 and CD44 prevent clinical disease by partially targeting the primary influx of encephalitogenic T cells and by preventing the secondary influx of leukocytes to lesions initiated by the transferred T cells.

Animals↗
PubMed2003

Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid arthritis.

There is intense interest in mechanisms whereby low-grade inflammation could interact with conventional and novel vascular risk factors to promote the atheromatous lesion. Patients with rheumatoid arthritis (RA), who by definition manifest persistent high levels of inflammation, are at greater risk of developing cardiovascular disease. Mechanisms mediating this enhanced risk are ill defined. On the basis of available evidence, we argue here that the systemic inflammatory response in RA is critical to accelerated atherogenesis operating via accentuation of established and novel risk factor pathways. By implication, long-term suppression of the systemic inflammatory response in RA should be effective in reducing risk of coronary heart disease. Early epidemiological observational and clinical studies are commensurate with this hypothesis. By contrast, risk factor modulation with conventional agents, such as statins, may provide unpredictable clinical benefit in the context of uncontrolled systemic inflammatory parameters. Unraveling such complex relationships in which exaggerated inflammation-risk factor interactions are prevalent may elicit novel insights to effector mechanisms in vascular disease generally.

Arthritis, Rheumatoid↗
PubMed2006

Macrophage migration inhibitory factor: controller of systemic inflammation.

Macrophage migration inhibitory factor (MIF) is a cytokine that is secreted by the anterior pituitary and immune cells in response to surgical stress, injury, and sepsis. This cytokine appears to be a critical regulator of the inflammatory pathways, leading to systemic inflammatory response syndrome and subsequent multiple organ dysfunction syndrome. This report provides an integrated scheme describing the manner by which MIF controls the neurohormonal response and the adaptive immune system, namely the T-helper (Th)1 and Th2 lymphocytes, which results in the release of pro-inflammatory cytokines and the anti-inflammatory cytokine interleukin-10. The development of systemic inflammatory response syndrome and subsequent development of multiple organ dysfunction syndrome appear to be related to MIF levels and the balance of Th1 and Th2 function.

Humans↗