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Low-grade Inflammation (low-grade + inflammation)
Selected AbstractsSoluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapyJOURNAL OF MEDICAL VIROLOGY, Issue 2 2008Ove Andersen Abstract Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected patients, reflecting possibly a low-grade pro-inflammatory state. Low-grade inflammation has been implicated in insulin resistance and other features of dysmetabolism. Accordingly it is hypothesized that circulating suPAR is associated with the metabolic status of HIV-infected patients on HAART. Fasting plasma suPAR was determined in 36 normoglycaemic HIV-infected patients on HAART (n,=,18 lipodystrophic, and n,=,18 non-lipodystrophic) who had estimated insulin sensitivity (Rd) and non-oxidative glucose disposal (NOGM) by euglycaemic hyperinsulinaemic clamps, indirect calorimetry, and glucose tracer infusion. Five patients had circadian suPAR concentrations measured (24 hr, 20 min-intervals). suPAR and non-HDL-cholesterol were higher and Rd, NOGM, and limb fat were lower in lipodystrophic patients than in non-lipodystrophic patients (P,<,0.05). suPAR correlated positively with non-HDL-cholesterol and inversely with Rd, NOGM and limb fat (P,<,0.005, n,=,36). suPAR also correlated positively with leukocyte count and TNF-, (P,<,0.01, n,=,36) but not with IL-6. In multiple regression analyses suPAR was a stronger predictor of dysmetabolism than TNF-, and IL-6. Circadian suPAR did not systematically fluctuate. In conclusion, suPAR may reflect the metabolic status of the HIV-infected patient on HAART, thus linking low-grade inflammation, immune constitution, lipid and glucose metabolism, and fat redistribution. Circadian suPAR concentration appeared stable, suggesting that sampling schedule does not affect measurement. Further studies addressing whether suPAR predicts lipodystrophy and dysmetabolism in HIV-infected patients are warranted. J. Med. Virol. 80:209,216, 2008. © 2007 Wiley-Liss, Inc. [source] Inflamed adipose tissue, insulin resistance and vascular injuryDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2008Christian X. Andersson Abstract Type 2 diabetes is the most common metabolic disorder today and has reached epidemic proportions in many countries. Insulin resistance and inflammation play a central role in the pathogenesis of type 2 diabetes and are present long before the onset of the disease. During this time, many of the complications associated with type 2 diabetes are initiated. Of major concern is the two- to fourfold increase in cardiovascular morbidity and mortality in this group compared to a nondiabetic population. Obesity, characterized by enlarged fat cells, and insulin resistance are, like type 2 diabetes, associated with impaired adipogenesis and a low-grade chronic inflammation that to a large extent emanates from the adipose tissue. Both these processes contribute to unfavourable alterations of the circulating levels of several bioactive molecules (adipokines) that are secreted from the adipose tissue, many of which have documented inhibitory effects on insulin sensitivity in the liver and peripheral tissues and, in addition, have negative effects on the cardiovascular system. Here we review current knowledge of the adipose tissue as an endocrine organ, the local and systemic effects of a chronic state of low-grade inflammation residing in the adipose tissue, and, in particular, the effects of inflammation and circulating adipokines on the vascular wall. Copyright © 2008 John Wiley & Sons, Ltd. [source] Impaired glucose regulation and type 2 diabetes in children and adolescentsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2008Kerstin Kempf Abstract Diabetes mellitus in paediatric patients used to be almost exclusively type 1, but in recent years, case series as well as hospital-based and population-based studies indicated that the number of children and adolescents with type 2 diabetes (T2DM) has been increasing. This development is alarming since T2DM in youth is usually not an isolated condition, but accompanied by other cardiovascular risk factors such as obesity, dyslipidaemia, hypertension and low-grade inflammation. In adults, numerous studies provided detailed data on prevalence, incidence and risk factors for the development of T2DM, but for children and adolescents clinical and experimental data are still rather limited. This review provides an overview about the epidemiology and pathogenesis of T2DM in youth and about impaired glucose regulation as major risk factor for diabetes development with a special focus on the recent literature on clinical and lifestyle-related risk factors. Differences in incidence and prevalence across different populations indicate that ethnic background and genetic pre-disposition may be important risk determinants. In addition, epigenetic factors and foetal programming appear to confer additional risk before birth. Among the environmental and lifestyle-related risk factors there is evidence that obesity, hypercaloric diet, physical inactivity, socio-economic position (SEP), smoking, low-grade inflammation, psychosocial stress and sleeping patterns contribute to the risk for T2DM. However, the assessment of the relevance of risk factors and of incidence or prevalence estimates in youth is complicated by methodological issues that are also discussed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Association of components of the metabolic syndrome with the appearance of aggregated red blood cells in the peripheral blood.DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005An unfavorable hemorheological finding Abstract Background Components of the metabolic syndrome are associated with low-grade inflammation. This can be accompanied by the synthesis of sticky proteins and erythrocyte aggregation. Methods The degree of erythrocyte aggregation was evaluated by a simple slide test and image analysis along with other markers of the acute-phase response, including the white blood cell count (WBCC), erythrocyte sedimentation rate (ESR), fibrinogen and high sensitivity C-reactive protein (hs-CRP) concentrations. Patients were categorized in four groups according to the absence or presence of 1, 2 and 3 or more components of the metabolic syndrome. Results We examined a total of 1447 individuals (576 women and 871 men) who gave their informed consent for participation. A significant cardiovascular risk factors, age and hemoglobin adjusted correlation was noted between the degree of erythrocyte aggregation and the number of components of the metabolic syndrome (r = 0.17, p < 0.0005). This correlation was better than that observed for clottable fibrinogen (r = 0.13 p < 0.0005), for ESR (r = 0.11 p < 0.0005) or WBCC (r = 0.13 p < 0.0005). A somewhat better correlation was noted for hs-CRP (r = 0.26 p < 0.0005). Conclusions The multiplicity of components of the metabolic syndrome is associated with enhanced erythrocyte aggregation, probably related to the presence of multiple adhesive macromolecules in the peripheral blood. The enhanced aggregation might contribute to capillary slow flow, tissue deoxygenation as well as vasomotor tone changes in the presence of multiple components of this syndrome. Copyright © 2004 John Wiley & Sons, Ltd. [source] Peripheral arterial disease in diabetes,a reviewDIABETIC MEDICINE, Issue 1 2010E. B. Jude Diabet. Med. 27, 4,14 (2010) Abstract Diabetic patients are at high risk for peripheral arterial disease (PAD) characterized by symptoms of intermittent claudication or critical limb ischaemia. Given the inconsistencies of clinical findings in the diagnosis of PAD in the diabetic patient, measurement of ankle-brachial pressure index (ABI) has emerged as the relatively simple, non-invasive and inexpensive diagnostic tool of choice. An ABI < 0.9 is not only diagnostic of PAD even in the asymptomatic patient, but is also an independent marker of increased morbidity and mortality from cardiovascular diseases. With better understanding of the process of atherosclerosis, avenues for treatment have increased. Modification of lifestyle and effective management of the established risk factors such as smoking, dyslipidaemia, hyperglycaemia and hypertension retard the progression of the disease and reduce cardiovascular events in these patients. Newer risk factors such as insulin resistance, hyperfibrinogenaemia, hyperhomocysteinaemia and low-grade inflammation have been identified, but the advantages of modifying them in patients with PAD are yet to be proven. Therapeutic angiogenesis, on the other hand, represents a promising therapeutic adjunct in the management of PAD in these patients. Outcomes after revascularization procedures, such as percutaneous transluminal angioplasty and surgical bypasses in diabetic patients, are poorer, with increased perioperative morbidity and mortality compared with that in non-diabetic patients. Amputation rates are higher due to the distal nature of the disease. Efforts towards increasing awareness and intensive treatment of the risk factors will help to reduce morbidity and mortality in diabetic patients with PAD. [source] Menstrual cycle symptoms are associated with changes in low-grade inflammationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2006J. J. Puder Abstract Background, A close link between mood, low-grade inflammation and obesity has been demonstrated even in healthy subjects. We investigated the relationship between changes in physical and psychological symptoms and inflammatory markers during the menstrual cycle both in normal weight and in overweight women. Materials and methods, Eight healthy normal weight (body mass index 21·6 ± 1·9 kg m,2) and seven overweight (body mass index 30 ± 2·4 kg m,2) young women with normal ovarian function and with no premenstrual syndrome were assessed 15 times throughout their menstrual cycle. At each time point fasting blood was drawn and symptoms were recorded using the Freeman Daily Symptom Record. Results, Independent of weight status, the serum concentrations of highly sensitive C-reactive protein (hs-CRP) and the total scores, in addition to the individual four factors (mood, behaviour, pain and physical symptoms), of the Daily Symptom Record varied significantly during the menstrual cycle (all P , 0·04) and paralleled each other. During the menstrual cycle, repeated hs-CRP serum concentrations correlated to the corresponding total symptom score and the factors mood, behaviour and physical symptoms, independent of both weight status and changes in circulating gonadal steroids (all P , 0·04). These associations were not observed for tumour necrosis factor-, serum levels. The mean hs-CRP concentrations were associated with the mean total symptom score, independent of weight status (r = 0·56, P = 0·04). Conclusion, Healthy young women showed psychological and physical symptoms during the menstrual cycle which changed in association with alterations in low-grade inflammation and which were independent of body weight or plasma levels of gonadal steroids. [source] Weight reduction, but not a moderate intake of fish oil, lowers concentrations of inflammatory markers and PAI-1 antigen in obese men during the fasting and postprandial stateEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2004A. Jellema Abstract Background, In obese subjects, chronic low-grade inflammation contributes to an increased risk of metabolic abnormalities, which are reversed by weight loss. Sustained weight loss, however, is difficult to achieve and more insight into dietary approaches on anti-inflammatory responses in obese subjects is needed. In this respect, fish oil deserves attention. Material and methods, Eleven obese men (BMI: 30,35 kg m,2) received daily fish oil (1·35 g n-3 fatty acids) or placebo capsules in random order for 6 weeks. Eight subjects continued with a weight reduction study that lasted 8 weeks. Mean weight loss was 9·4 kg. At the end of each experimental period a postprandial study was performed. Results, Relative to fasting concentrations, interleukin-6 (IL-6) levels increased by 75% 2 h and by 118% 4 h after the meal (P < 0·001), when subjects consumed the control capsules. In contrast, C-reactive protein (C-RP) concentrations decreased slightly by 0·7% and 6·6% (P = 0·046), and those of plasminogen activator inhibitor-1 (PAI-1) antigen by, respectively, 26% and 53% (P < 0·001). Tumour necrosis factor-, (TNF-,; P = 0·330) and soluble TNF-receptor concentrations (sTNF-R55 and sTNF-R75; P = 0·451 and P = 0·108, respectively) did not change. Changes relative to fasting concentrations were not significantly affected by either fish oil or weight reduction. Absolute IL-6, C-RP, sTNF-R55, sTNF-R75, and PAI-1 antigen concentrations, however, were consistently lower after weight reduction, but not after fish oil consumption. Conclusion, For slightly obese subjects a moderate intake of fish oil does not have the same favourable effects on markers for a low-grade inflammatory state as weight reduction. [source] Muscle Strength After Resistance Training Is Inversely Correlated with Baseline Levels of Soluble Tumor Necrosis Factor Receptors in the Oldest OldJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 2 2004Helle Bruunsgaard MD Objectives:, To test the hypothesis that physical exercise induces an antiinflammatory response that is associated with reduced chronic activation of the tumor necrosis factor (TNF)-alpha system in frail elders and that the increase in muscle strength after resistance training is limited by systemic low-grade inflammation. Design:, A 12-week controlled resistance-training study. Setting:, Nursing homes in Copenhagen, Denmark. Participants:, Twenty-one frail nursing home residents aged 86 to 95 completed the study. Intervention:, Ten participants were randomized to a program of resistance training of knee extensors and flexors three times a week for 12 weeks; the remaining 11 participants served as a control group who joined social activities supervised by an occupation therapist. Measurements:, Muscle strength, plasma levels of TNF-,, soluble TNF receptor (sTNFR)-1, and interleukin (IL)-6 were measured before and at the end of the intervention period. Results:, The training program improved muscle strength but did not affect plasma levels of TNF-, and sTNFR-I or IL-6. However, plasma levels of sTNFR-I at baseline were inversely correlated with the increase in muscle strength. Conclusion:, Low-grade activation of the TNF system could limit the increase in muscle strength after resistance training in the oldest old. Furthermore, data suggest that theantiinflammatory response induced by 12 weeks of resistance training is not sufficient to reduce chronic activation of the TNF system, but the small sample size limited this interpretation. [source] Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapyJOURNAL OF MEDICAL VIROLOGY, Issue 2 2008Ove Andersen Abstract Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected patients, reflecting possibly a low-grade pro-inflammatory state. Low-grade inflammation has been implicated in insulin resistance and other features of dysmetabolism. Accordingly it is hypothesized that circulating suPAR is associated with the metabolic status of HIV-infected patients on HAART. Fasting plasma suPAR was determined in 36 normoglycaemic HIV-infected patients on HAART (n,=,18 lipodystrophic, and n,=,18 non-lipodystrophic) who had estimated insulin sensitivity (Rd) and non-oxidative glucose disposal (NOGM) by euglycaemic hyperinsulinaemic clamps, indirect calorimetry, and glucose tracer infusion. Five patients had circadian suPAR concentrations measured (24 hr, 20 min-intervals). suPAR and non-HDL-cholesterol were higher and Rd, NOGM, and limb fat were lower in lipodystrophic patients than in non-lipodystrophic patients (P,<,0.05). suPAR correlated positively with non-HDL-cholesterol and inversely with Rd, NOGM and limb fat (P,<,0.005, n,=,36). suPAR also correlated positively with leukocyte count and TNF-, (P,<,0.01, n,=,36) but not with IL-6. In multiple regression analyses suPAR was a stronger predictor of dysmetabolism than TNF-, and IL-6. Circadian suPAR did not systematically fluctuate. In conclusion, suPAR may reflect the metabolic status of the HIV-infected patient on HAART, thus linking low-grade inflammation, immune constitution, lipid and glucose metabolism, and fat redistribution. Circadian suPAR concentration appeared stable, suggesting that sampling schedule does not affect measurement. Further studies addressing whether suPAR predicts lipodystrophy and dysmetabolism in HIV-infected patients are warranted. J. Med. Virol. 80:209,216, 2008. © 2007 Wiley-Liss, Inc. [source] Review article: uncomplicated diverticular disease of the colonALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006L. PETRUZZIELLO Summary Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect healthcare costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed. [source] Anthropometric indices as predictors of the metabolic syndrome and its components in adolescentsPEDIATRICS INTERNATIONAL, Issue 3 2010Christian Jung Abstract Background:, Overweight and related health problems are becoming increasingly recognized, especially in children and adolescents. For early screening, different anthropometrical measurements of obesity have been proposed to identify individuals at risk. We compared body mass index (BMI), BMI standard deviation score, waist circumference, waist-to-hip ratio (WHR), and waist/height ratio with respect to their power to predict the metabolic syndrome, its components and low-grade inflammation. Methods:, A total of 79 male Caucasian German adolescents (13,17 years) were studied. All anthropometrical measurements of obesity were recorded and blood samples drawn. Predictive power was estimated using receiver operating characteristic curves, by comparing the area under the curve (AUC). Results:, Except for WHR, all tested anthropometrical measurements of obesity showed comparably good AUC values for correct prediction, with the highest AUC for BMI (P < 0.001, AUC = 0.885 ± 0.039). Superior prediction power was not observed for BMI standard deviation score, waist circumference, WHR or waist/height ratio. Furthermore, BMI was the best predictor of elevated C-reactive protein levels as a marker for low-grade inflammation (P < 0.001, AUC = 0.786 ± 0.064). Conclusions:, In this cross-sectional study the well-established parameter BMI was shown to have the best predictive power to identify metabolic syndrome, its components and markers for low-grade inflammation. Newly developed parameters did not provide superior values. Future longitudinal studies are needed to compare these anthropometrical markers in larger cohorts, incorporating different age groups and ethnic backgrounds. [source] Hemostatic and thrombotic markers in patients with hemoglobin E/,-thalassemia diseaseAMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2007Pantep Angchaisuksiri Increased frequency of thrombosis has been observed in patients with hemoglobin E/,-thalassemia (Hb E/,-thal) disease, particularly those who have previously been splenectomized. We compared various hemostatic and thrombotic markers in blood from 15 Hb E/,-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin, ,2 thromboglobulin, C-reactive protein, tissue plasminogen activator antigen were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 were significantly higher in the S than in the NC group. Levels of plasminogen activator inhibitor-1 antigen were significantly higher in the S than in the NS group. Levels of protein C, protein S, antithrombin, and fibrinogen were significantly lower in the S and NS groups than in the NC group. Plasma lipoprotein(a) levels in the S and NS groups were not statistically different from NC. Our findings indicated that there is evidence of chronic low-grade coagulation and platelet activation, chronic low-grade inflammation, endothelial cell injury, impaired fibrinolysis, and decreased naturally occurring anticoagulants in splenectomized Hb E/,-thal patients. These changes may account for the increased risk of thrombosis in these patients. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Change in waist circumference over 11 years and current waist circumference independently predict elevated CRP in Filipino women,AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Julienne N. Rutherford C-reactive protein, a marker of chronic, low-grade inflammation, is strongly associated with current central adiposity, and has been linked to elevated risk of cardiovascular disease. Less is known about the contribution of longitudinal change in waist circumference to current inflammation. We evaluated the extent to which current waist circumference and change over an 11-year interval contribute independently to low-grade systemic inflammation measured in a group of 1,294 women, 35,69 years, participating in the Cebu Longitudinal Nutrition and Health Survey in the Philippines. Waist circumference was measured at the time of blood draw for CRP analysis in 2005 and during an earlier survey in 1994. A waist circumference delta variable was constructed by subtracting current circumference from past circumference. We used logistic regression models to predict having an elevated plasma CRP concentration (3 mg L,1 < CRP < 10 mg L,1). Waist circumference in 2005 was a strong predictor of elevated CRP (OR 1.10, 95% CI = 1.08, 1.12, P < 0.001). In combined models, increase in circumference over 11 years was a significant and independent predictor of elevated CRP risk (OR = 1.023, 95% CI = 1.00, 1.05, P < 0.05). Considering the average increase over time, the cumulative risk of elevated CRP due to increased central adiposity was 25.7%. However, women who reduced their waist circumference between 1994 and 2005 had greatly reduced risk (6.2%), suggesting that even long-term inflammatory burden can be reversed by weight loss. Although current waist circumference is an important contributor to risk of elevated systemic inflammation in this as in other populations, history of central adiposity may be an independent phenomenon. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc. [source] Intrinsic subtype-associated changes in the plasma proteome in breast cancerPROTEOMICS - CLINICAL APPLICATIONS, Issue 11 2009Harikrishna Nakshatri Abstract Breast cancers are classified into five intrinsic subtypes: Luminal subtype A, Luminal subtype B, HER2+, Basal, and Normal-like. In this study, we compared the plasma proteome of patients with Luminal A, Luminal B, HER2+, and Basal subtype with plasma from healthy individuals. Protein changes were considered significant if q -value (false discovery rate) was less than 5%. The highest number of changes in the plasma proteome was observed in patients with Luminal type B followed by Basal type breast cancers. The plasma proteome of Luminal A and HER2+ breast cancer patients did not differ significantly from healthy individuals. In Basal breast cancer, a significant number of plasma proteins were downregulated compared with healthy individuals. Acute phase-response proteins ,-glycoprotein orosomucoid 1 and serum amyloid protein P were specifically upregulated in the plasma of Luminal B breast cancer patients, suggesting prevalence of low-grade inflammation. Proteins involved in immune response and free radical scavenging were downregulated in the plasma of Luminal B patients, which is in agreement with defective immune system observed in cancer patients. These results reveal intrinsic subtype specific changes in the plasma proteome that may influence tumor progression as well as the systemic effects of cancer. [source] Chondrocyte innate immune myeloid differentiation factor 88,dependent signaling drives procatabolic effects of the endogenous toll-like receptor 2/toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in miceARTHRITIS & RHEUMATISM, Issue 7 2010Ru Liu-Bryan Objective Toll-like receptor 2 (TLR-2)/TLR-4,mediated innate immunity serves as a frontline antimicrobial host defense, but also modulates tissue remodeling and repair responses to endogenous ligands released during low-grade inflammation. We undertook the present study to assess whether the endogenous TLR-2/TLR-4 ligands low molecular weight hyaluronan (LMW-HA) and high mobility group box chromosomal protein 1 (HMGB-1), which are increased in osteoarthritic (OA) joints, drive procatabolic chondrocyte responses dependent on TLR-2 and TLR-4 signaling through the cytosolic adaptor myeloid differentiation factor 88 (MyD88). Methods We studied mature femoral head cap cartilage explants and immature primary knee articular chondrocytes from TLR-2/TLR-4,double-knockout, MyD88-knockout, and congenic wild-type mice. Generation of nitric oxide (NO), degradation of hyaluronan, release of HMGB-1, matrix metalloproteinase 3 (MMP-3), and MMP-13, and protein expression of type X collagen were assessed by Griess reaction and Western blotting analyses. Expression of messenger RNA for type II and type X collagen, MMP-13, and RUNX-2 was examined by real-time quantitative reverse transcription,polymerase chain reaction. Results Interleukin-1, and TLR-2 and TLR-4 ligands induced both HMGB-1 release from chondrocytes and extracellular LMW-HA generation in normal chondrocytes. TLR-2/TLR-4,/, and MyD88,/, mouse cartilage explants and chondrocytes lost the capacity to mount procatabolic responses to both LMW-HA and HMGB-1, demonstrated by >95% suppression of NO production (P < 0.01), and attenuated induction of MMP-3 and MMP-13. Combined deficiency of TLR-2/TLR-4, or of MyD88 alone, also attenuated release of NO and blunted induction of MMP-3 and MMP-13 release. MyD88 was necessary for HMGB-1 and hyaluronidase 2 (which generates LMW-HA) to induce chondrocyte hypertrophy, which is implicated in OA progression. Conclusion MyD88-dependent TLR-2/TLR-4 signaling is essential for procatabolic responses to LMW-HA and HMGB-1, and MyD88 drives chondrocyte hypertrophy. Therefore, LMW-HA and HMGB-1 act as innate immune cytokine-like signals with the potential to modulate chondrocyte differentiation and function in OA progression. [source] Low-grade systemic inflammation in patients with amyotrophic lateral sclerosisACTA NEUROLOGICA SCANDINAVICA, Issue 6 2009D. Keizman Objective,,, To prospectively determine the intensity of systemic low-grade inflammation in patients with amyotrophic lateral sclerosis (ALS). Patients and methods,,, Patients with ALS and matched healthy controls underwent blood tests for inflammation-sensitive biomarkers: erythrocyte sedimentation rate (ESR), quantitative fibrinogen, wide-range C-reactive protein (wrCRP) concentrations, leukocyte count and neutrophil-to-lymphocyte ratio (NLR). The correlation between these inflammatory biomarkers and disability status of the patients, expressed by the ALS Functional Rating Scale (ALSFRS-R), was evaluated. Results,,, Eighty patients with ALS and 80 matched controls were included. wrCRP, fibrinogen, ESR and NLR values were significantly elevated in patients compared with controls. There was a significant correlation between the ALSFRS-R score and wrCRP, ESR and fibrinogen levels. This correlation persisted on sequential examinations. Conclusions,,, A systemic low-grade inflammation was detected in patients with ALS and correlated with their degree of disability. A heightened systemic inflammatory state is apparently associated with a negative prognosis in ALS. [source] | |||||||||||||