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IL-6 Concentrations (il-6 + concentration)
Selected AbstractsPlasma IL-6 concentration is inversely related to insulin sensitivity, and acute-phase proteins associate with glucose and lipid metabolism in healthy subjectsDIABETES OBESITY & METABOLISM, Issue 6 2005M. K. Heliövaara Aim:, It has been shown that atherosclerosis is an inflammatory disease. Recent data suggest that inflammation precedes type 2 diabetes. Hence, we wanted to study the interrelationship between IL-6, insulin sensitivity, lipids and numerous acute-phase proteins. Methods:, Twenty-one healthy individuals [16 males/5 females, age 27.9 ± 1.8 years, body mass index (BMI) 24.1 ± 0.8 kg/m2] participated in the study. Each patient went through a 4-h hyperinsulinaemic (40 mU/m2/min) euglycaemic clamp and 4-h saline infusion. Blood samples were taken before and at the end of the infusions. Results:, Plasma interleukin (IL)-6 concentration correlated inversely with insulin sensitivity (M -value) (r = ,0.49, p < 0.05). Moreover, the plasma levels of IL-6 associated with c-peptide (r = 0.49, p < 0.05), fat% (r = 0.43, p < 0.05) and diastolic blood pressure (r = 0.46, p < 0.05). ,-1-acid glycoprotein was related to HbA1c (r = 0.47, p < 0.05), insulin (r = 0.55, p < 0.01), diastolic blood pressure (r = 0.58, p < 0.01), systolic blood pressure (r = 0.58, p < 0.01) and triglycerides (r = 0.58, p < 0.01). Haptoglobin was correlated with insulin (r = 0.46, p < 0.05), total cholesterol (r = 0.61, p < 0.01), BMI (r = 0.58, p < 0.01), fat% (r = 0.63, p < 0.01) and lipid oxidation during clamp (r = 0.43, p < 0.05). Diastolic blood pressure decreased during the clamp (from 78.3 ± 1.9 to 72.1 ± 2.0 mmHg, p = 0.001). Insulin infusion did not affect the serum levels of most acute-phase proteins. Conclusions:, Our study suggests that low grade inflammation, as reflected by IL-6, A1GP and haptoglobin contributes to the regulation of insulin sensitivity, lipid metabolism and blood pressure in normal human physiology. [source] The extent of periodontal disease and the IL-6,174 genotype as determinants of serum IL-6 levelJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 12 2007Taina Raunio Abstract Aim: To study the extent of periodontal disease and the IL-6,174 genotype as determinants of serum and mouthwash IL-6 concentration in subjects with moderate to severe periodontal disease. Material and Methods: Fifty-two generally healthy subjects volunteered to participate. Probing pocket depth (PD) and periodontal attachment level (AL) were clinically examined and alveolar bone level (BL) was measured on orthopantomographs. IL-6 concentrations in mouthwash, collected by rinsing with 3 ml saline for 30 s and in serum, obtained by venipuncture, were measured using ELISA. IL-6,174 polymorphism was studied using a polymerase chain reaction. Results: Eleven subjects carried the GG genotype, and 41 subjects, carried the CG/CC genotype. The mean (± SD) concentration of IL-6 in serum was 1.6 (± 1.5) pg/ml and, 2.8 (± 5.04) pg/ml in mouthwash. The serum concentration of IL-6 was higher in subjects with the GG genotype than with the CG/CC genotype. In regression analyses the percentages of sites with PD6 mm, AL6 mm and BL8 mm, the IL-6,174 genotype, body mass index and gender associated significantly with serum IL-6 concentration. Conclusions: The extent of moderate to severe periodontal disease and the IL-6,174 genotype contribute significantly to serum IL-6 concentration. [source] ORIGINAL ARTICLE: Profile of Peripheral Blood Neutrophil Cytokines in Diabetes Type 1 Pregnant Women and its Correlation with Selected Parameters in the NewbornsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010Magdalena Perty, ska-Marczewska Citation Perty,ska-Marczewska M, G,owacka E, Grodzicka A, Sobczak M, Cypryk K, Wilczy,ski JR., Wilczy,ski J. Profile of peripheral blood neutrophil cytokines in diabetes type 1 pregnant women and its correlation with selected parameters in the newborns. Am J Reprod Immunol 2010; 63: 150,160 Problem, Interleukin (IL)-12, IL-10, tumor necrosis factor-, (TNF-,), IL-6 and IL-8 alter as pregnancy progresses, implying continuous immune regulation associated with the maintenance of pregnancy. We aimed to evaluate the peripheral blood neutrophil-derived production of these cytokines in the course of pregnancy complicated by type 1 diabetes. Method of study, These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (P) and pregnant diabetic (PD) women. Results, Neutrophil-derived secretion of TNF-, and IL-12 increased along with progression of pregnancy in PD and P groups. The concentration of IL-10 from lipopolysaccharide (LPS)-stimulated neutrophils increased during the course of uncomplicated pregnancy but decreased in diabetic pregnancy. Concentration of IL-8 decreased with the advancing gestational age in P and PD groups. LPS-stimulated neutrophil-derived IL-6 concentration increased only in PD patients. Conclusion, Our results show that diabetes creates pro-inflammatory environment thus potentially influencing the outcome of pregnancy. We conclude that neutrophil-derived cytokine production could contribute to the complications seen in pregnant women with type 1 diabetes. [source] Combination of cervical interleukin-6 and -8, phosphorylated insulin-like growth factor-binding protein-1 and transvaginal cervical ultrasonography in assessment of the risk of preterm birthBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2001Merja Kurkinen-Räty Objective To determine the value of combinations of cervical interleukin-6 (IL-6), cervical interleukin-8 (IL-8), the phosphorylated isoform of insulin-like growth-factor binding protein-1 (IGFBP-1), and cervical ultrasonography in the prediction of preterm birth. Design Prospective follow up. Setting Oulu University Hospital maternity clinic from February 1997 to July 1998. Population Women with singleton pregnancies (n= 77), referred from outpatient clinics at 22,32 weeks of gestation with symptoms (uterine contractions) or signs (cervical change) of threatened preterm birth. Symptomless women (n= 78) matched for gestational age, parity and maternal age at recruitment were studied as a reference group. Methods A urine sample for bacterial culture was collected, and cervical swab samples for assays of interleukin-6 and -8 and phoshorylated IGFBP-1 were taken before digital cervical examination. A Pap smear for analysis of bacterial vaginosis and samples for analysis of chlamydia and streptococci were also obtained. Cervical measurements were made by transvaginal ultrasonography. The same sampling and cervical measurement were repeated twice at two-week intervals. The cutoff values of the markers were determined by receiver-operating characteristic curve analysis. Main outcome measure Preterm birth (<37 weeks). Results The preterm birth (<37 weeks) rate for women in the study group was 16% (12/77). The cervical interleukin-6 cutoff value (61 ng/L) at first visit had a sensitivity of 73% and a specificity of 61% in predicting preterm birth, with a positive likelihood ratio (LR+) of 1.9 (95% CI 1.2,3.0). An ultrasonographically measured cervical index value of > 0.36 at recruitment predicted preterm birth in 25% (5/20) of the study group compared with 9% (5/54); LR+ 2.2 (95% CI 1.03,4.7). Cervical phosphorylated IGFBP-1 > 6.4,g/L [LR+ 1.8 (95% CI 0.7,2.9)], interleukin-8 > 3739 ng/L [LR+ 1.4 (95% CI 0.9,2.4)], and ultrasonograpic cervical length < 29.3 mm [LR+ 2.7 (95% CI 0.8,9.7)] increased the risk of preterm birth. According to the logistic regression model, a combination of IL-6, and IL-8 and cervical index increased the specificity to 97%, but the sensitivity fell to 30% in detecting preterm birth. There was a significantly increased incidence of puerperal infections if phosphorylated IGFBP-1 concentrations were elevated (> 21.0 ,g/L), 36% (4/11) compared with 4.6% (3/65), LR+ 6.7 (95% CI 2.7,17), the sensitivity being 67% (4/6) and the specificity 90% (63/70). Elevated phosphorylated IGFBP-1 concentrations (> 21.6,g/L) were also associated with an increased risk of neonatal infections; LR+ 8.0 (95% CI 3.5,18). Conclusions An increase in cervical IL-6 concentration and the ultrasonographically measured cervical index appear to be associated with preterm birth. A combination of these markers with measurement of cervical IL-8 appears to be the best predictor of preterm birth. Neither the sensitivity nor specificity of the tests used in this study are good enough to predict preterm birth for clinical decision making. Cervical phosphorylated IGFBP-1 seems to be a marker of puerperal and neonatal infectious morbidity in cases of threatened preterm delivery, suggesting early tissue degradation at the choriodecidual interface. [source] IL-6 levels decrease with SSRI treatment in patients with major depressionHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2005Ayse Devrim Basterzi Abstract Objective Some evidence indicates that an immune response with an increased production of proinflammatory cytokines often accompanies major depression. The objective of this study was to examine the serum levels of IL-6 in patients with major depression and the changes occurring in IL-6 levels during treatment with selective serotonin reuptake inhibitors (SSRI). Method Twenty-three patients with a DSM-IV diagnosis of major depressive disorder and 23 healthy matched controls were included in the study. The severity of depression was measured with the Hamilton rating scale for depression. Blood samples for IL-6 levels were obtained at baseline and at week 6 of treatment and IL-6 concentrations were evaluated using a solid phase sandwich enzyme immunoassay. All patients were treated with an SSRI. Results The IL-6 levels showed no statistically significant difference between the patients and the controls at baseline. However, IL-6 levels after treatment with SSRIs were significantly lower compared with the baseline IL-6 levels of both the patients and the controls. Conclusion The results of this study suggest that proinflammatory cytokines show some changes during the course of treatment of major depression. These findings might also be considered as supporting the hypothesis of a modulatory role of antidepressants on the immune system. Copyright © 2005 John Wiley & Sons, Ltd. [source] Chronic Cytomegalovirus Infection and Inflammation Are Associated with Prevalent Frailty in Community-Dwelling Older WomenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2005Heidi N. Schmaltz MDCM Objectives: To evaluate the association between asymptomatic chronic cytomegalovirus (CMV) infection and the frailty syndrome and to assess whether inflammation modifies this association. Design: Cross-sectional analysis. Setting: Women's Health and Aging Study I & II, Baltimore, Maryland. Participants: Seven hundred twenty-four community-dwelling women aged 70 to 79 with baseline measures of CMV, interleukin-6 (IL-6), and frailty status. Measurements: CMV serology and IL-6 concentrations were measured using enzyme-linked immunosorbent assay. Frailty status was based on previously validated criteria: unintentional weight loss, weak grip strength, exhaustion, slow walking speed, and low level of activity. Frail women had three or more of the five components, prefrail women had one or two components, and women who were not frail had none of the components. Multinomial logistic regression adjusted for potential confounders. Results: Eighty-seven percent of women were CMV seropositive, an indication of chronic infection. CMV was associated with prevalent frailty, adjusting for age, smoking history, elevated body mass index, diabetes mellitus, and congestive heart failure (CMV frail adjusted odds ratio (AOR)=3.2, P=.03; CMV prefrail AOR=1.5, P=.18). IL-6 interacted with CMV, significantly increasing the magnitude of this association (CMV positive and low IL-6 frail AOR=1.5, P=.53; CMV positive and high IL-6 frail AOR=20.3, P=.007; CMV positive and low IL-6 prefrail AOR=0.9, P=.73; CMV positive and high IL-6 prefrail AOR=5.5, P=.001). Conclusion: Chronic CMV infection is associated with prevalent frailty, a state with increased morbidity and mortality in older adults; inflammation enhances this effect. Further prospective studies are needed to establish a causal relationship between CMV, inflammation, and frailty. [source] The extent of periodontal disease and the IL-6,174 genotype as determinants of serum IL-6 levelJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 12 2007Taina Raunio Abstract Aim: To study the extent of periodontal disease and the IL-6,174 genotype as determinants of serum and mouthwash IL-6 concentration in subjects with moderate to severe periodontal disease. Material and Methods: Fifty-two generally healthy subjects volunteered to participate. Probing pocket depth (PD) and periodontal attachment level (AL) were clinically examined and alveolar bone level (BL) was measured on orthopantomographs. IL-6 concentrations in mouthwash, collected by rinsing with 3 ml saline for 30 s and in serum, obtained by venipuncture, were measured using ELISA. IL-6,174 polymorphism was studied using a polymerase chain reaction. Results: Eleven subjects carried the GG genotype, and 41 subjects, carried the CG/CC genotype. The mean (± SD) concentration of IL-6 in serum was 1.6 (± 1.5) pg/ml and, 2.8 (± 5.04) pg/ml in mouthwash. The serum concentration of IL-6 was higher in subjects with the GG genotype than with the CG/CC genotype. In regression analyses the percentages of sites with PD6 mm, AL6 mm and BL8 mm, the IL-6,174 genotype, body mass index and gender associated significantly with serum IL-6 concentration. Conclusions: The extent of moderate to severe periodontal disease and the IL-6,174 genotype contribute significantly to serum IL-6 concentration. [source] Maternal circulating interferon-, and interleukin-6 as biomarkers of Th1/Th2 immune status throughout pregnancyJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2008Aziz Aris Abstract Aim:, T cells may be classified as T helper type 1 (Th1) cells, which synthesize cytokines inducing cellular immunity, or T helper type 2 (Th2), which synthesize cytokines inducing humoral immunity. According to the Th1/Th2 paradigm, it has been postulated that successful pregnancy induces an immune Th2 bias, but it is not yet clear how Th1 and Th2 systems vary simultaneously throughout the pregnancy. Methods:, Using maternal circulating interferon-, (IFN-,) and interleukin-6 (IL-6) as biomarkers of Th1 and Th2 cytokines, respectively, we examined the variation of circulating Th1/Th2 ratio in 35 healthy pregnant women from 10 to 40 weeks of pregnancy. Results:, With increasing gestational age, maternal circulating levels of IFN-, decrease, whereas those of IL-6 increase. The IFN-,/IL-6 ratio switches around the 19th week of pregnancy. Conclusions:, Our results suggest that maternal systemic IFN-, and IL-6 concentrations may be biomarkers of Th1/Th2 immune status during pregnancy. Moreover, our findings showed that contrary to the Th1/Th2 paradigm, the Th1 bias may be prevailing at the beginning of pregnancy, balanced in the middle of pregnancy and supplanted by the Th2 bias at the end of pregnancy. [source] Insulin alters cytokine content in two pivotal organs after brain death: a porcine modelACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2008A. BARKLIN Background: To optimize the quantity and quality of organs available for transplantation, it is crucial to gain further insight into the treatment of brain dead organ donors. In the current study we hypothesized that insulin treatment after brain death alters cytokine content in the heart, liver, and kidney. Methods: Sixteen brain dead pigs (35,40 kg) were treated with either (1) no insulin [brain dead without insulin treatment treatment (BD)], or (2) insulin infusion intravenously (i.v.) at a constant rate of 0.6 mU/kg/min during 360 min [brain dead with insulin treatment (BD+I)]. Blood glucose was clamped at 4.5 mmol/l by infusion of 20% glucose. Blood samples for insulin, glucose, catecholamines, free fatty acids, and glucagon were obtained during the experimental period. Six hours after brain death biopsies were taken from the heart, liver, and kidney. These were analyzed for cytokine mRNA and proteins [tumor necrosis factor-, (TNF-,), interleukin (IL)-6, and IL-10]. Results: The BD+I compared with the BD animals had lower IL-6 concentrations in the right ventricle of the heart (P=0.001), in the renal cortex (P=0.04) and in the renal medulla (P=0.05), and lower IL-6 mRNA in the renal medulla (P=0.0002). Furthermore, the BD+I animals had lower concentrations in the renal medulla of IL-10 (P=0.01), and tended to have lower TNF-, in the renal cortex (P=0.06) than the BD animals. In the right ventricle of the heart TNF-, mRNA and IL-10 mRNA were higher in the BD+I than in the BD group (P=0.002 and 0.004). Conclusion: Insulin has anti-inflammatory effects on cytokine concentration in the heart and kidney after brain death. [source] Post-natal Changes in Testicular Concentrations of Interleukin-1 Alpha and Beta and Interleukin-6 during Sexual Maturation in BullsREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2010ET Bagu Contents Based on observations in laboratory animals interleukins could be regulators of testicular development. The objects of this study were to see if interleukins (IL-1 and IL-6) are present in the developing bull testis and to establish the temporal patterns of concentrations of IL-1 and IL-6 in the bovine testis during development. Separate groups of six bull calves were castrated every 4 weeks from 5 to 33 weeks of age, and at 56 weeks of age. Mean testicular IL-1 alpha concentrations decreased (p < 0.01) from 5 to 9 weeks of age and 13 to 21 weeks of age. Mean testicular IL-1 beta concentrations decreased (p < 0.01) from 13 to 17 weeks of age and from 29 to 33 weeks of age. Mean IL-1 bioactivity increased from 13 to 17 weeks of age, decreased to 21 weeks, increased to 25 weeks, decreased to 29 weeks and decreased from 33 to 56 weeks of age (p < 0.05). Mean testicular IL-6 concentrations decreased (p < 0.05) from 9 to 13 weeks of age, increased (p < 0.05) to 21 weeks, decreased (p < 0.05) to 25 weeks, increased (p < 0.05) to 29 weeks and decreased (p < 0.01) to 56 weeks of age. In conclusion, testicular IL-1 alpha, IL-1 beta and IL-6 were found in the bovine testis and concentrations were age dependent. Testicular IL-1 alpha and IL-1 beta concentrations were highest in the early post-natal period; however, IL-1 bioactivity and IL-6 concentrations were greatest in the immediate pre-pubertal period. These findings suggest a functional role for interleukins in testicular development in the bull. [source] Mycobacterial heat shock protein-induced blood T lymphocytes subsets and cytokine pattern: Comparison of sarcoidosis with tuberculosis and healthy controlsRESPIROLOGY, Issue 3 2007Anna DUBANIEWICZ Background and objective: Sarcoidosis (SA) is a disorder of unknown aetiology. Mycobacterium tuberculosis heat shock proteins (Mtb-hsp) have been considered as causative agents of SA. The role of Mtb-hsp in the immune response in SA has not been investigated. Methods: Mtb-hsp-stimulated T-cell subsets and Th1/Th2 cytokine patterns in the supernatant from peripheral blood mononuclear cell cultures from 22 SA patients, 20 tuberculosis (TB) patients and 20 healthy volunteers were compared using flow cytometry. Results: In unstimulated cultures, a significantly higher percentage of CD8+,,+T-cells were present in SA versus controls. Similarly there was a significantly increased IL-6 and decreased IL-4 level in SA and significantly lower INF-,, IL-2, IL-4, IL-10 production in TB versus controls. After Mtb-hsp stimulation, there was a significantly increased TNF-,, IL-6, IL-10 and decreased INF-,, IL-2, IL-4 production in SA and significantly increased TNF-,, IL-6 concentrations in TB versus controls. CD8+,,+IL-4+T-cells were detected significantly less often in Mtb-hsp-induced cultures in SA versus controls. Comparing SA versus TB, CD4+,,+TCR-cells were significantly increased in Mtb-hsp-induced cultures in TB versus controls and SA. Before stimulation, significantly increased IL-6, IL-10 and decreased IL-4 level in SA versus TB was revealed, whereas Mtb-hsp stimulation caused significantly increased IL-10 and decreased IL-4 concentrations in SA. Conclusions: After Mtb-hsp stimulation, increased levels of pro-inflammatory cytokines, TNF-, and IL-6 were found in sera from SA and TB patients in comparison with healthy controls; SA patients demonstrated the lowest levels of IL-4 and the highest levels of IL-10. [source] Comparison of Vaginal Cytokine Collection MethodsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2006Constance J. Faro Objective The objective of our study was to correlate the interleukin-6 (IL-6) concentrations detected in patient-collected specimens with provider-collected specimens and compare the reproducibility of the methods. Study design All enrolled participants underwent pelvic examination with collection of cytokine samples by the provider and also collected samples themselves using vaginal swabs. The order of sample collection was randomly assigned. All samples were frozen at ,80°C for batch analysis. A commercial enzyme-linked immunosorbent assay was used to determine the concentrations of IL-6 in all samples. Results IL-6 concentrations from wicks and swabs were correlated in a linear fashion (r = 0.67, P < 0.001). IL-6 concentrations in the two swabs (r = 0.94, P < 0.001) and the two wicks (r = 0.71, P < 0.001) were correlated in a linear fashion, although there was more variability in wick specimens. Conclusion IL-6 concentrations can be reproducibly measured using either method. The ease of patient swab collection and the correlation with provider-collected specimens may make frequent assessment of the vaginal cytokine environment more acceptable to patients. [source] META060 inhibits osteoclastogenesis and matrix metalloproteinases in vitro and reduces bone and cartilage degradation in a mouse model of rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 6 2010Veera Reddy Konda Objective The multikinase inhibitor META060 has been shown to inhibit NF-,B activation and expression of markers of inflammation. This study was undertaken to investigate the effect of META060 on biomarkers associated with bone and cartilage degradation in vitro and its antiinflammatory efficacy in vivo in both acute and chronic inflammation models. Methods Glycogen synthase kinase 3, (GSK3,),dependent ,-catenin phosphorylation was evaluated in RAW 264.7 macrophages to assess kinase inhibition. The inhibition of osteoclastogenesis and tartrate-resistant acid phosphatase (TRAP) activity was evaluated in RANKL-treated RAW 264.7 cells. The inhibition of interleukin-1, (IL-1,),mediated markers of inflammation was analyzed in human rheumatoid arthritis synovial fibroblasts (RASFs). Mice with carrageenan-induced acute inflammation and collagen-induced arthritis (CIA) were used to assess efficacy. Results META060 inhibited the activity of kinases (spleen tyrosine kinase [Syk], Bruton's tyrosine kinase [Btk], phosphatidylinositol 3-kinase [PI 3-kinase], and GSK3) associated with RA and inhibited ,-catenin phosphorylation. META060 inhibited osteoclastogenesis, as indicated by decreased transformation of RAW 264.7 cells to osteoclasts and reduced TRAP activity, and inhibited IL-1,,activated prostaglandin E2, matrix metalloproteinase 3, IL-6, IL-8, and monocyte chemotactic protein 1 in RASFs. In mice with acute inflammation, oral administration of META060 reduced paw swelling similar to the effect of aspirin. In mice with CIA, META060 significantly reduced the arthritis index and decreased bone, joint, and cartilage degradation. Serum IL-6 concentrations in these mice were inhibited in a dose-dependent manner. Conclusion Our findings indicate that META060 reduces swelling in a model of acute inflammation and inhibits bone and cartilage destruction in a model of chronic inflammation. Its efficacy is associated with the inhibition of multiple protein kinases, including Syk, Btk, PI 3-kinase, and GSK3. These results warrant further clinical testing of META060 for its therapeutic potential in the treatment of inflammatory diseases. [source] Role of placenta growth factor and its receptor flt-1 in rheumatoid inflammation: A link between angiogenesis and inflammationARTHRITIS & RHEUMATISM, Issue 2 2009Seung-Ah Yoo Objective To investigate the direct effects of placenta growth factor (PlGF) and its specific receptor, flt-1, which are known to mediate angiogenesis, on the inflammatory process of rheumatoid arthritis (RA). Methods Expression of PlGF and flt-1 in the synovial tissue of RA patients was examined using immunohistochemistry. Enzyme-linked immunosorbent assay was used to determine the concentrations of PlGF, tumor necrosis factor , (TNF,), and interleukin-6 (IL-6) in culture supernatants of either mononuclear cells or synoviocytes. The flt-1 expression level in mononuclear cells was analyzed by flow cytometry. Experimental arthritis was induced in mice either by immunization with type II collagen (CII) or by injection of anti-CII antibody. Results PlGF was highly expressed in the synovium of RA patients, and its primary source was fibroblast-like synoviocytes (FLS). When stimulated with IL-1,, FLS from RA patients produced higher amounts of PlGF than did FLS from patients with osteoarthritis. Exogenous PlGF specifically increased the production of TNF, and IL-6 in mononuclear cells from RA patients (but not those from healthy controls) via a calcineurin-dependent pathway. The response to PlGF was associated with increased expression of flt-1 on RA monocytes, which could be induced by IL-1, and TNF,. A novel anti,flt-1 hexapeptide, GNQWFI, abrogated the PlGF-induced increase in TNF, and IL-6 production, and also suppressed CII-induced arthritis and serum IL-6 concentrations in mice. Moreover, genetic ablation of PlGF prevented the development of anti-CII antibody,induced arthritis in mice. Conclusion Our data suggest that enhanced expression of PlGF and flt-1 may contribute to rheumatoid inflammation by triggering production of proinflammatory cytokines. The use of the novel anti,flt-1 peptide, GNQWFI, may be an effective strategy for the treatment of RA. [source] Alteration of inflammatory response following small-volume resuscitationBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000F. Gebhard Background Small-volume resuscitation is rather effective in the primary volume treatment of major trauma. Blood pressure stabilizing effects occur immediately but last for a limited period only. Influences on inflammatory reactions in humans have not been reported so far. This prospective randomized study therefore analysed the inflammatory response in the very early (pre)clinical period after administration of crystalloids plus starch, hyperosmolar/hyperoncotic starch and lyophilized plasma solutions. Methods Upon approval of the ethics committee, 41 patients were enrolled with multiple injuries (injury severity score (ISS) mean 34 (range 9,75)). The patients received randomly either standard solutions, i.e. starch plus crystalloids (group C (control); n = 14), hyperosmolar/hyperoncotic starch (group S (small volume); n = 14) or lyophilized plasma (group L (lyoplasma); n = 13). Subsets were performed according to the different solutions as well as to the severity of trauma (ISS below 17, 18,31, 32 or more) and survivors/non-survivors. The first blood sample was obtained at the scene of the accident before cardiopulmonary resuscitation, when appropriate. Subsequently, blood samples were collected hourly. All samples were spun immediately at 4°C and stored at ,70°C. Interleukin (IL) 6 as well as several different prostaglandins (PGI2, thromboxane A2, PGE2) were determined to characterize the overall inflammatory response. Results Eleven casualties (seven men and four women, mean age 31 years) died because of major trauma within 24 h after the incident. In all patients IL-6 levels promptly increased within the first 2 h, most pronounced in patients with the severest trauma (ISS greater than 32) and non-survivors. Patients in groups C and S had a comparable time course of IL-6 plasma levels with a slightly higher release in minor injuries (ISS less than 30). The same was true for prostaglandins. In contrast, patients in group L had clearly higher IL-6 concentrations during the first 2,12 h, again most pronounced in those with the severest trauma (ISS greater than 32). Conclusion These results demonstrate that the early systemic inflammatory response after small-volume resuscitation is rather similar to that of patients infused with standard-volume therapy after trauma. In contrast, lyoplasma seems to increase the inflammatory response regardless of the injury severity. © 2000 British Journal of Surgery Society Ltd [source] The effect of NQO1 polymorphism on the inflammatory response in cardiopulmonary bypassCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2008C. Selim Isbir Abstract Cardiopulmonary bypass (CPB) has been associated with systemic inflammatory response syndrome (SIRS). Endothelial dysfunction related to non-laminar flow during CPB is known to play a key role in this complex pathology. Antioxidant response element (ARE) dependent NAD(P)H:quinone oxidoreductase 1 (NQO1) promoter is a regulatory element involved in the anti-inflammatory mechanism in vasculature exposed to non-laminar flow. Mutation of the NQO1 could represent a novel anti-inflammatory effect in CPB. The goal of this study was to demonstrate whether genetic variants of NQO1 affect cytokine release after CPB. Eighteen patients who underwent standard coronary artery bypass grafting (CABG) operation were included in the study. Genotyping for NQO1 was performed. Serum Interleukin-6 (IL-6) levels were measured before induction, during CPB after declamping the aorta, and 24,h after operation. Clinical data were collected respectively. Seven patients were NQO1 T carriers and 11 patients were NQO1 T non-carriers. During CPB, IL-6 concentrations were increased in NQO1 T carriers compared to T non-carriers (p,=,0.038). Although ventilation times and blood loss were higher in T carriers these were not statistically significant. Patients with NQO1 T carriers showed significantly higher IL-6 levels during CPB. Non-laminar flow during CPB may diminish the transcriptional activation of the NQO1 in T carriers. Preoperative determination of this novel anti-inflammatory mechanism could be useful to improve operative outcome in CPB. Copyright © 2007 John Wiley & Sons, Ltd. [source] Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN- ,, IL-4, IL-10 and IL-13) in patients with allergic asthmaCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2001C. K. Wong Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have been suggested to play an important role in the induction and maintenance of the inflammatory cascade in allergic asthma. We compared the plasma concentrations of novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon- , (IFN- ,) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age-matched health control subjects. Plasma cytokines were measured by enzyme-linked immunosorbent assay. Intracellular cytokines were quantified by flow cytometry. Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in allergic asthmatic patients than normal control subjects (IL-18: median 228·35 versus 138·72 pg/ml, P < 0·001; IL-12: 0·00 versus 0·00 pg/ml, P = 0·001; IL-10: 2·51 versus 0·05 pg/ml, P < 0·034; IL-13: 119·38 versus 17·89 pg/ml, P < 0·001). Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations than normal controls (22·40 versus 11·86 pg/ml and 3·42 versus 0·61 pg/ml, respectively), although the differences were not statistically significant (P = 0·077 and 0·053, respectively). The percentage of IFN- , -producing Th cells was significantly higher in normal control subjects than asthmatic patients (23·46 versus 5·72%, P < 0·001) but the percentage of IL-4 producing Th cells did not differ (0·72 versus 0·79%, P > 0·05). Consequently, the Th1/Th2 cell ratio was significantly higher in normal subjects than asthmatic patients (29·6 versus 8·38%, P < 0·001). We propose that allergic asthma is characterized by an elevation of both proinflammatory and Th2 cytokines. The significantly lower ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic asthma. [source] Bacterial translocation in a non-lethal rat model of peritonitisCOLORECTAL DISEASE, Issue 5 2001V. Yao Background Bacterial translocation from the gut may occur under a variety of different clinical circumstances and has been implicated in the development of multiple organ failure. The aim of this study was to determine the distribution of bacterial translocation occurring in a model of chemically induced peritonitis. We also sought to document the degree of the associated immune and inflammatory response. Methods Though a midline laparotomy, rats were injected with 5 mg of zymosan (in 0.2 ml of saline) into the subomental space. After 4, 18, 24, 48 and 96 h, a number of endpoints evaluated: intraperitoneal cellular influx, TNF-, and interleukin-6 concentrations and myeloperoxidase activity. Bacterial cultures were initiated from the free peritoneal fluid, mesenteric lymph nodes, liver, lung, and kidney. Imprints were also made of the peritoneal mesothelial surface to determine its integrity. Results When comparing rats injected with zymosan with the controls, there was evidence of a peritoneal inflammatory response within 4 hours. Facultative gram negative bacteria were found to be growing in the mesenteric lymph nodes and in the peritoneal fluid at 48 h. Anaerobic organisms were also cultured from the peritoneal fluid at 48 h. No organisms were cultured from the liver, lung or kidneys. In addition there was a significant increase in intraperitoneal cell numbers (predominantly neutrophils, P < 0.05), myeloperoxidase activity (P < 0.05) and TNF-, and IL-6 concentrations (P < 0.05). There was extensive loss of the peritoneal mesothelial cells. The peritoneal inflammatory changes and bacterial translocation had resolved by 96 h. Conclusion Bacterial translocation can be induced by the presence of an acute inflammatory focus in the peritoneal cavity. The translocation and inflammatory changes were associated with extensive loss of mesothelial cells. Nonetheless, these changes all resolved, indicating that the peritoneal cavity has a significant capacity to deal with such insults. A clearer understanding of the cellular and molecular events involved in the resolution phase could lead to improvements in the treatment of peritonotis. [source] |