Differences In Interleukin-6 Concentrations Research Articles

Relationship between latent left ventricular contractile dysfunction and signs of immune inflammation in patients with COVID-19 pneumonia

Aim. To investigate the relationship between echocardiographic parameters and laboratory immune inflammation signs in patients after coronavirus disease 2019 (COVID-19) pneumonia depending on the left ventricular (LV) involvement according to speckle tracking echocardiography (STE).Material and methods. The study included 216 patients (men, 51,1%, mean age, 50,1±11,1 years). The examination was carried out in patients 3 months after COVID-19 pneumonia. Patients were divided in 3 groups: group I (n=41) — diffuse decrease (≥4 segments the same LV level) of longitudinal strain (LS) according to STE; group II (n=67) — patients with regional decrease (LS reduction ≥3 segments corresponding to systems of the anterior, circumflex or right coronary arteries); group III — patients without visual left ventricle involvement (n=108).Results. There were no significant differences in LV ejection fraction — 68,9±4,1% in group I, 68,5±4,4% in group II and 68,6±4,3 in group III (p=0,934). A decrease in the global longitudinal left ventricle strain was detected significantly more often in groups I and II compared with group III (-17,8±2,0, -18,5±2,0 and -20,8±1,8%, respectively; p<0,001). At the same time, LS depression of LV basal level (-14,9±1,5, -16,8±1,2% and -19,1±1,7%; p<0,001), as well as a decrease in LS of LV inferior-posterior segments in group with diffuse involvement was detected significantly more often than in groups II and III. In addition, we revealed a significant difference in interleukin-6 concentration — 3,1 [2,5;4,0], 3,1 [2,4;3,8] and 2,5 [3,8;1,7] pg/ml, (p=0,033), C-reactive protein — 4,0 [2,2;7,9], 5,7 [3,2;7,9] and 2,4 [1,1;4,7] mg/l, (p<0,001), tumor necrosis factor-a — 5,9±1,9, 6,2±1,9 and 5,2±2,0 pg/ml, (p=0,004) and ferritin — 130,7 [56,5;220,0], 92,2 [26,0;129,4] and 51,0 [23,2;158,9] pg/l, respectively (p=0,025).Conclusion. A relationship was found between diffuse and regional left ventricular involvement according to STE and signs of immune inflammation in patients 3 months after COVID-19 pneumonia.

Development of a Rat Model of Intra-Amniotic Inflammation via Ultrasound-Guided Administration of a Triggering Agent in the Gestational Sac to Enable Analysis of Individual Amniotic Fluid Samples.

Objectives: To develop a rat model of intra-amniotic inflammation, characterized by the concentration of interleukin-6 in the amniotic fluid, induced by an ultrasound-guided transabdominal administration of lipopolysaccharide into individual gestational sacs. Methods: An ultrasound-guided transabdominal intra-amniotic administration of lipopolysaccharide or phosphate-buffered saline (PBS) as control was performed in rats on embryonic day 18. Only accessible gestational sacs with precise recording of their positions were injected. Twenty-four hours later, individual amniotic fluid samples were collected from the gestational sacs of laparotomized animals. The gestational sacs were divided into four subgroups: (i) with lipopolysaccharide: injected gestational sacs from rats undergoing lipopolysaccharide administration; (ii) without lipopolysaccharide: non-injected gestational sacs from rats undergoing lipopolysaccharide administration; (iii) with PBS: injected gestational sacs from rats undergoing PBS administration; and (iv) without PBS: non-injected gestational sacs from rats undergoing PBS administration. The concentration of interleukin-6 in individual amniotic fluid samples was assessed using ELISA. Results: In the group of five animals receiving lipopolysaccharide, 24 (33%) and 48 (77%) gestational sacs were and were not injected, respectively. The amniotic fluid was obtained from 21 (88%) injected and 46 (95%) non-injected sacs. In the control group of five animals receiving phosphate-buffered saline, 28 (35%) and 52 (75%) gestational sacs were and were not injected, respectively. The amniotic fluid was obtained from 18 (64%) injected and 50 (96%) non-injected sacs. No labor occurred, and only one fetal death was observed in a gestational sac injected with lipopolysaccharide. Differences in concentrations of interleukin-6 in the amniotic fluid were found among the subgroups of the gestational sacs (with lipopolysaccharide: median 762 pg/ml; without lipopolysaccharide: median 35.6 pg/ml; with PBS: median 35.6 pg/ml; and without PBS: median 35.6 pg/ml; p < 0.0001). Concentrations of interleukin-6 in the amniotic fluid from the gestational sacs with lipopolysaccharide were significantly higher than those in the three remaining subgroups (p < 0.0001). No differences in concentrations of interleukin-6 in the amniotic fluid were identified between the three remaining subgroups. Conclusion: The ultrasound-guided transabdominal intra-amniotic administration of lipopolysaccharide with a subsequent collection and analysis of amniotic fluid samples is feasible in rats. The intra-amniotic administration of lipopolysaccharide led to the development of intra-amniotic inflammation without leading to fetal mortality or induction of labor.

Predictive model using hemoglobin, albumin, fibrinogen, and neutrophil-to-lymphocyte ratio to distinguish patients with colorectal cancer from those with benign adenoma.

Colorectal cancer (CRC) is associated with inflammation, activation of coagulation, and mild anemia. Hematological parameters reflecting ongoing cancer may have the potency to be effective for early diagnostics of CRC. The aim of this study was to examine the validity and relationship between some biochemical and hematological parameters for the early diagnosis of CRC. We designed a prospective observational cohort study to analyze whether these laboratory markers have the potency to distinguish benign tumors from malignant before planned surgery. The clinical data were collected from 208 patients with suspected benign or malignant colorectal tumors who were eligible for elective surgery between September 2018 and January 2020. Blood samples were collected one day before surgery, examined parameters included: complete blood count, hemoglobin (HGB) concentration, albumin (ALB), C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen (FG). Absolute neutrophil and lymphocyte counts were used for the calculation of the neutrophil-to-lymphocyte ratio (NLR). The diagnosis was confirmed by histopathological examination. The 197 patients were divided into the group of benign (B group = 52 patients) or malignant tumors (CRC group = 145 patients). ROC curves and cut-off values of NLR, HGB, FG, and ALB concentration, serum CRP and IL-6 levels. In the cohort of 197 adult patients submitted for the elective colorectal surgery, the complete blood samples drawn one day before surgery showed significant differences between patients with benign tumors and colorectal carcinoma: HGB (mean 139.9 g/l vs. 129.9; p<0.001), FG (mean 3.36 g/l vs. 3.94 g/l; p<0.001), ALB (mean 43.4 g/l vs. 41.1 g/l; p=0.001), NLR (mean 2.73 vs. 3.88; p=0.016), respectively. CRP (mean 2.9 mg/l vs. 4.4 mg/l; p=0.011), thrombocyte count (mean 235×109/l vs. 265×109/l; p<0.029). Differences in IL-6 concentrations were not significant (2.9 pg/ml vs. 4.15 pg/ml; p=0.052). Using multivariable logistic regression analysis, four valid parameters (HGB, FG, ALB, and NLR) were suitable for the construction of a diagnostic predictive model for the identification of CRC. In conclusion, a panel of routinely examined blood parameters like HGB, FG, ALB, and NLR has the potency to distinguish patients with benign tumors from malignant by applying a diagnostic predictive model for early laboratory detection of CRC.

Associations between IL-6 and Echo-Parameters in Patients with Early Onset Coronary Artery Disease.

Background: Over the last two decades, many studies have investigated the association between interleukin 6 (IL-6) and pathogenesis and progression of coronary artery disease (CAD). Patients with CAD manifested at a young age are a particularly interesting group. They differ from older patients, not only in terms of the severity of coronary artery atherosclerosis, but also risk factor profiles, short- and long-term prognosis after myocardial infarction (MI). The role of IL-6 in younger patients with CAD is less well-known. Therefore, our study aimed to analyze the relationship between IL-6 level and other inflammations, atherosclerosis, and cardiac function parameters in early onset CAD patients. Methods: The study covered 100 patients with early onset CAD and a group of 50 healthy participants. Plasma levels of IL-6 and basic biochemical parameters, anthropometric, echocardiographic, and arteries Doppler ultrasound measurements were performed. Results: We did not observe a significant difference in IL-6 concentration in plasma between patients with early onset CAD and a control group, but IL-6 level was negatively correlated with echocardiographic measurements of ascending aorta diameter, left ventricular shortening fraction, and right ventricular end-diastolic diameter in our patients. Conclusions: In patients with early onset CAD, plasma IL-6 level is associated with other inflammation parameters and with cardiac function, potentially contributing to right ventricular remodeling and left ventricular systolic dysfunction. This suggests possible prognostic benefits of long-time observation of IL-6 level after the acute coronary syndrome.

Developing a method of co‐incubating murine adipocytes and macrophages for evaluating cellular communication

Adipose tissue, an organ containing both adipocytes and adipose tissue macrophages (ATMs), secretes cytokines known as adipokines. Of these two cell types, ATMs have a larger role in the production and release of proinflammatory adipokines. The objective of this research was to develop a system of co‐incubating adipocytes and macrophages that allowed us to quantitatively measure the cross‐talk between these two cell types. Nitric Oxide (NO) and interleukin‐6 (IL‐6) concentrations were quantified to determine macrophage activation and production of a proinflammatory adipokine, respectively. Leptin concentrations were used as a measure of adipocyte‐specific adipokine production. The cell lines used were RAW 264.7 (murine macrophages) and 3T3‐L1 (murine fibroblasts). 3T3‐L1 fibroblasts were differentiated into adipocytes, which was confirmed by the presence of lipid droplets. Transwell plates with permeable inserts were used to co‐incubate the macrophages and adipocytes; the confluent adipocytes were maintained in the 12‐well plate (lower compartment) and the macrophages were added to the transwell insert (upper compartment). Macrophages were stimulated with 0.01 mg/ml of LPS either before or after the addition of the the macrophages to the insert. The treatments were: 3T3+media, 3T3+media+LPS, 3T3+unstimulatedRAW, 3T3+RAW+LPS, 3T3+stimulatedRAW (in fresh media), and 3T3+stimulatedRAW (in conditioned media). There was no difference in IL‐6 concentration measured in the upper compartment of the transwell insert vs the lower compartment, while measured NO levels were higher in the upper compartment and leptin levels were higher in the lower compartment (p&lt;0.001, matched pairs t‐test). The 3T3+RAW+LPS, 3T3+stimulatedRAW (in fresh media) and 3T3+stimulatedRAW (in conditioned media) co‐incubation protocols resulted in the highest concentration of IL‐6 (p=0.0006). The 3T3+RAW+LPS and 3T3+stimulatedRAW (in conditioned media) co‐incubation methods yielded the highest concentrations of NO in both the upper and bottom compartments of the plate (p&lt;0.001). There was no difference in leptin concentrations due to co‐incubation protocol. There was a positive relationship between NO and IL‐6 in both the top and bottom compartments (p&lt;0.001, linear regression) and between NO and leptin in the top (p=0.03) but not in the bottom compartment. There was no significant relationship between IL‐6 and leptin concentrations in either the top or bottom compartments. For future experiments, our lab will utilize the co‐incubation protocols that resulted in the highest production of NO and IL‐6: 3T3+RAW+LPS and 3T3+stimulatedRAW (in conditioned media).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The role of interleukin-6 in pathogenesis of chronic periapical lesions

Summary Introduction Cytokine network plays an important role in pathogenesis of chronic periapical lesions. The aim of this study was to determine the concentration of interleukin-6 (IL-6) in tissue homogenates of human periapical lesions and correlate its levels with symptomatology and size of the lesions. Materials and Methods 93 samples of chronic periapical lesions were obtained after extraction of teeth. Samples were divided according to the clinical presentation as symptomatic and asymptomatic, and according to the size as large and small. The concentration of IL-6 was analyzed using ELISA. Results Statistically significant difference in IL-6 concentration was observed in symptomatic lesions compared to asymptomatic (p&lt;0.001). Analysis showed statistically higher concentration in large symptomatic lesions compared to large asymptomatic lesions (p&lt;0.001), and in small symptomatic lesions compared to small asymptomatic (p&lt;0.05). Higher production of IL-6 was observed in large lesions compared to small but this difference was not statistically significant. Conclusion Higher concentration of IL-6 in lesions with expressed clinical symptoms as well as in large lesions indicates that IL-6 is an important factor responsible for the progression of lesions and bone resorption.

Serum level of interleukin-6 (IL-6) and N-terminal propeptide of procollagen type I (PINP) in patients with liver diseases

Introduction: The aim of this study was to evaluate the concentration of interleukin-6 and N-terminal propeptide of procollagen type I and their relationship in liver diseases of different etiologies.Material and methods: Serum samples were obtained from 30 healthy volunteers and patients suffering from alcoholic cirrhosis (AC) – 31, non-alcoholic cirrhosis (NAC) – 28 and toxic hepatitis (HT) – 23 patients. Cirrhotic patients were classified according to Child–Pugh score. IL-6 and PINP concentrations were determined according to the electrochemiluminescence immunoassay.Results: The mean serum IL-6 concentration was significantly higher in AC (mean ± SD:21.52 ± 15.01 pg/mL), NAC (20.07 ± 32.12 pg/mL) and HT (15.14 ± 17.18 pg/mL) when compared to the control group (C) (1.67 ± 0.42 pg/mL) (Mann–Whitney U test: p < .001 for all comparisons). The mean serum PINP concentration was significantly higher only in patients with AC (104.32 ± 54.50 ng/mL) in comparison with the control group (54.70 ± 19.83 ng/mL; p < .001). The mean values of IL-6 and PINP significantly differed between liver diseases (ANOVA rank Kruskal–Wallis test: p = .020 and p < .001, respectively). Accordingly, the serum levels of IL-6 and PINP were significantly higher in patients with AC than that in NAC (p < .001 and p = .022, respectively). IL-6 and PINP concentrations appeared to vary depending on the severity of liver damage (p < .001 for both). The concentrations of IL-6 and PINP were significantly higher in class C (31.88 ± 21.51 pg/mL; 132.73 ± 65.63 ng/mL, respectively) than that in class A (6.12 ± 9.00 pg/mL; 57.32 ± 28.85 ng/mL, respectively) (p < .001 for both). There were also significant differences in IL-6 concentrations between Child–Pugh class B (27.88 ± 24.45 pg/mL) and class A (6.12 ± 9.00 pg/mL; p < .001).Conclusions: We conclude that serum concentrations of IL-6 and PINP change in liver diseases, and those changes reflect the severity of liver disease.

Interleukin-6 concentrations in the urine and dipstick analyses were related to bacteriuria but not symptoms in the elderly: a cross sectional study of 421 nursing home residents.

BackgroundUp to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A complementary test to discriminate between symptomatic urinary tract infections (UTI) and ABU is needed, as diagnostic uncertainty is likely to generate significant antibiotic overtreatment. Previous studies indicate that Interleukin-6 (IL-6) in the urine might be suitable as such a test. The aim of this study was to investigate the association between laboratory findings of bacteriuria, IL-6 in the urine, dipstick urinalysis and newly onset symptoms among residents of nursing homes.MethodsIn this cross sectional study, voided urine specimens for culture, urine dipstick and IL-6 analyses were collected from all residents capable of providing a voided urine sample, regardless of the presence of symptoms. Urine specimens and symptom forms were provided from 421 residents of 22 nursing homes. The following new or increased nonspecific symptoms occurring during the previous month were registered; fatigue, restlessness, confusion, aggressiveness, loss of appetite, frequent falls and not being herself/himself, as well as symptoms from the urinary tract; dysuria, urinary urgency and frequency.ResultsRecent onset of nonspecific symptoms was common among elderly residents of nursing homes (85/421). Urine cultures were positive in 32% (135/421), Escherichia coli was by far the most common bacterial finding. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Residents with positive urine cultures had higher concentrations of IL-6 in the urine (p < 0.001). However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms.ConclusionsNonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. This study could not establish any clinical value of using dipstick urinalysis or IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms.

Assessment of Serum Myokines and Markers of Inflammation Associated with Exercise in Endurance Racing Sled Dogs

The endurance sled dog is the ultimate endurance athlete in which to examine the exercise-associated acute phase and myokine responses that might be related to changes in muscle metabolism and damage. An inciting cause for increased C-reactive protein has yet to be elucidated, which might involve interleukin-6 and other myokines. To examine concentrations of interleukin-6 (IL-6), interleukin-15 (IL-15), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), and markers of the inflammatory response of exercise; monocyte chemoattractant protein-1(MCP-1) and C-reactive protein (CRP) before, during, and after an endurance racing event. 26 sled dogs completing a 1650-km race. In a prospective study, cephalic venipuncture was performed before racing, at the midpoint, and after racing. Body weight and serum CRP, MCP-1, IL-15, IL-8, IL-6, and TNF-α concentrations were evaluated using enzyme-linked immunoabsorbance-based assays or a luminex multiplex assay. There were no significant differences in concentrations of IL-6, IL-15, IL-8, or TNF-α at the 3 time points, whereas there were significant increases in MCP-1 (median and range-start: 86pg/mL [30-1845]; midpoint: 179pg/mL [53-730]; finish: 180pg/mL [21-1294]; P<.01) and CRP (median and range-start: 18μg/mL [11-58]; midpoint: 76μg/mL [12-198]; finish: 60μg/mL [12-170]; P<.01) at the midpoint and race finish. There was a significant linear relationship between MCP-1 and IL-6 (R=0.68; P<.01). The inflammatory response to exercise increases as measured by MCP-1 during and after endurance exercise in sled dogs. IL-6 appears to be associated with MCP-1; however, the reasons for increases in the acute phase response (CRP) cannot be attributed to IL-6 or other myokines. IL-6 and MCP-1 concentrations might be useful in future investigations of exertional rhabdomyolysis.

Effects of Mycophenolic Acid on the Proliferation and Endothelin-1 and Interleukin-6 Secretion of Rat Pulmonary Microvascular Endothelial Cells

Objective: To investigate the effect of mycophenolic acid (MPA) on the proliferation of rat pulmonary microvascular endothelial cells (PMVECs) and on the secretion of endothelin-1 (ET-1) and interleukin-6 (IL-6) by these cells. Methods: Rat PMVECs were treated with five different final concentrations of MPA (0, 0.1, 1, 10 and 100 μM). The fetal bovine serum-induced proliferation of the PMVECs was detected using the Cell Counting Kit-8 (CCK-8). The levels of ET-1 and IL-6 secretion were assessed by radioimmunoassays. Results: At the 24 h time point, the optical density (OD) values at 450 nm for the five groups showed that there were no significant differences between the groups treated with 0 and 0.1 μM MPA (P=0.388) or between the groups treated with 10 and 100 μM MPA (P=0.292), but the OD values were significantly different between all other pairs of groups (P<0.001). At the 48 h time point, the OD values at 450 nm for the five groups showed that there was no significant difference between the groups treated with 0 and 0.1 μM MPA (P=0.094), but the OD values were significantly different between all the other groups (P<0.001). At the 72 h time point, the OD values at 450 nm for the five groups showed that there was no significant difference between the groups treated with the final concentrations of 0 and 0.1 μM MPA (P=0.931), but the OD values were significantly different between all other pairs of groups (10 μM MPA vs 100 μM MPA: P=0.037; 0 μM MPA vs 1 μM MPA: P=0.006; 1 μM MPA vs 10 μM MPA: P=0.005; all other comparisons: P<0.001). There were no significant differences in ET-1 concentration between the groups treated with 0 and 0.1 μM MPA (P=0.156) or the groups treated with 10 and 100 μM MPA (P=0.262), but there were significant differences between all other pairs of groups (P<0.001). By contrast, there were no significant differences in IL-6 concentrations between any pair of groups (P>0.05). Conclusions: MPA inhibits fetal bovine serum-induced rat PMVEC proliferation and ET-1 secretion in a dose-dependent manner.

IL-6 -174 C/C Genotype Is Not Conclusively a Low IL-6 Production Phenotype

TO THE EDITOR—We read with interest the article entitled “The interleukin 6 −174 C/C genotype predicts greater rhinovirus illness” [1]. The authors reported that among healthy adults, the interleukin 6 (IL-6) −174 C/C genotype was associated with greater symptom magnitudes after experimental rhinovirus type 39 infection. In the article, the IL-6 −174 C/C genotype was referred to as the phenotype with “low IL-6 production,” on the basis of “the convention published by Gentile and colleagues” [2]. Their study showed no significant difference in IL-6 concentrations in nasal secretions between the group with IL-6 −174 C/C genotype (n = 9) and those with wild type G/G and heterozygous polymorphic G/C combined (n = 47). IL-6 −174 polymorphic genotypes (G/C or C/C) have been reported to be functional; however, the literature on IL-6 production in cases with polymorphic genotypes has been controversial. Fishman et al [3] reported significantly lower levels of plasma IL-6 in healthy subjects with IL-6 −174 C/C genotype, compared with those with G/G or G/C genotypes. Similar findings have been reported in patients after coronary artery bypass surgery [4]. However, in other studies the results have been quite the opposite. Studies of adults with abdominal aneurysm [5] or coronary artery bypass surgery [6], as well as of children with thrombosis [7] and of healthy neonates [8], have reported higher levels of plasma IL-6 in participants with the IL-6 −174 C/C genotype, compared with carriers of the G allele. In 2 studies of healthy adults, no association was found between IL-6 −174 genotype and the level of plasma IL-6 [8, 9]. In vitro studies also show the controversy; IL-6 production by stimulated mononuclear cells of healthy adults with IL-6 −174 C/C genotype has either been low [10] or showed no difference in IL-6 production between different genotypes [8]. On the other hand, stimulation of cord blood neonatal monocytes resulted in higher IL-6 production in those with IL-6 −174 C/C genotype, compared with G/C or G/G genotype [8]. In our recent study, stimulation of adult monocytes with either lipopolysaccharide or respiratory syncytial virus resulted in significantly higher IL-6 production in the group of participants with polymorphic genotypes (G/C or C/C) than in wild-type (G/G) particpants [11]. Stimulation with rhinovirus, however, did not result in significant differences in IL-6 production between the genotype groups. The low prevalence of the IL-6 −174 C/C genotype did not allow us to independently compare IL-6 concentrations in heterozygous (G/C) and homozygous (C/C) polymorphic genotypes. In the study by Doyle et al, no statistically significant relationship was revealed between the IL-6 genotypes and IL-6 concentrations in nasal secretions [1]. Interestingly, the wild-type G/G genotype was combined with the heterozygote genotype and then compared with the C/C genotype. We wonder whether the results could be different if IL-6 production were compared among 3 different genotypes (G/G, G/C, and C/C) separately or the combined polymorphic genotypes (G/C with C/C) were compared with the wild-type genotype (G/G). In our previous study of risk for otitis susceptibility in children, we combined G/C with C/C; the polymorphic group had significantly higher risk for otitis susceptibility than did the G/G group [12]. Doyle et al reported that the subjects with IL-6 −174 C/C genotype had more upper respiratory infection days and higher symptom scores, compared with carriers of the G allele [1]. Their presumption of C/C genotype as a low cytokine production phenotype does not correlate with our understanding of the expected role of IL-6 as a proinflammatory cytokine that has been shown to be associated with greater severity of inflammatory disease. In our study showing a positive correlation between IL-6 −174 G/C and C/C polymorphisms and susceptibility to otitis media [12], we presumed that the polymorphic genotypes were high IL-6 producing and that the high cytokine concentrations enhanced the inflammation in nasopharyngeal and Eustachian tube mucosa during a viral upper respiratory infection, thereby increasing the risk for otitis media development. In summary, we agree with Doyle et al on the importance of the IL-6 −174 C/C genotype. The studies cited here, however, do not support the conclusion that the C/C genotype is “the low IL-6 production phenotype.”

Sex differences in inflammatory markers: what is the contribution of visceral adiposity?

BackgroundC-reactive protein (CRP) concentrations have been found to be higher in premenopausal women than in men, whereas interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations have been reported to be lower in women than in men. Objective:The objective was to determine whether the sex difference in body fat distribution accounts for the observed sex differences in inflammatory markers. Design:Plasma CRP, IL-6, and TNF-α concentrations were measured in 208 healthy men (age: 42.2 ± 15.2 y) and in 145 healthy women (age: 36.8 ± 11.1 y). Results:Compared with men, premenopausal women had higher CRP concentrations [1.24 (25th percentile: 0.54; 75th percentile: 3.04) compared with 0.94 (0.51, 2.40) mg/L; P < 0.05] and lower plasma TNF-α concentrations [1.50 (25th percentile: 1.23; 75th percentile: 1.82) compared with 1.71 (1.40, 2.05) pg/mL; P < 0.001]. No sex difference in IL-6 concentrations was noted. Regression analyses indicated that the relation between CRP or IL-6 and visceral adipose tissue (VAT) and subcutaneous AT (SAT) was sex-specific; a significantly steeper slope was observed in women than in men (P < 0.05). Sex differences in CRP concentrations were abolished after SAT was adjusted for. In a multivariate model of the whole sample, we found that both SAT and VAT and the sex × SAT interaction term were significant correlates of CRP and IL-6 concentrations. Finally, whereas CRP concentrations were largely influenced by visceral adiposity in men, subcutaneous adiposity was the key correlate of CRP in women. Conclusion:The higher CRP concentrations found in women appear to be due to their greater accumulation of subcutaneous fat than that observed in men.

Aortic aneurysms secrete interleukin-6 into the circulation

Circulating plasma interleukin-6 (IL-6) concentrations are elevated in patients with abdominal aortic aneurysms (AAAs) compared with controls. In vitro studies suggest that the aneurysm is the source of the IL-6. Because IL-6 is an independent risk factor for cardiovascular mortality, elevation of this cytokine may be significant in these patients, who represent a group at increased risk from cardiovascular death. The aim of this study was to directly measure in vivo aortic IL-6 concentrations, testing the hypothesis that aneurysms secrete IL-6 into the circulation. Before endovascular aneurysm repair took place, blood was sampled from the entire length of the aorta in 27 patients with AAA and nine with thoracic aneurysms (TAs). A control group consisted of 15 patients without aneurysms undergoing angiography. Plasma IL-6 was determined using enzyme-linked immunosorbent assay, and high-sensitivity C-reactive protein (hs-CRP) was measured turbidimetrically. Aneurysm surface area was calculated from axial computed tomography scans. Mean IL-6 concentrations (pg/mL) were higher in the TA and AAA groups compared with controls (10.4 +/- 3.7 and 4.9 +/- 0.5 vs 2.7 +/- 0.5, P = .002). There was a significant difference in plasma IL-6 concentration corresponding to aneurysm position in the AAA (P = .002) and TA (P = .008) groups, with both patterns conforming to a linear trend. This pattern was not observed in the control group, in which no significant difference in IL-6 concentrations was found throughout the aorta. Peak IL-6 occurred earlier in TAs compared with AAAs (descending aorta vs iliac artery) corresponding to aneurysm position (P = .0007). Linear regression revealed a positive correlation between aneurysm surface area and mean plasma IL-6 (Spearman's correlation, P = .003). The mean surface areas of the TAs, at 0.07 m2 (interquartile range [IQR], 0.06 to 0.09), were higher than those of the AAAs at 0.03 m2 (IQR, 0.02 to 0.04; P = .002). High-sensitivity CRP was within normal limits, and no significant differences were found between the AAA group and the controls. Circulating IL-6 is elevated within the aorta in patients with aneurysms and corresponds to aneurysm position. Furthermore, aneurysm surface area and mean plasma IL-6 are correlated. In the absence of any evidence of systemic inflammation in the form of elevated hs-CRP, these data support the hypothesis that aneurysms secrete IL-6 into the circulation. This may contribute to the high cardiovascular mortality observed in patients with aneurysms.

Umbilical cord interleukin‐6 levels are elevated in term neonates with perinatal asphyxia

A correlation between elevation of pro-inflammatory cytokines and white matter injury or abnormal neurologic outcome has been established in the preterm infant. In the full-term neonate, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. Our aims were to investigate if serum interleukin-6 concentrations in delivering mothers and their offspring at birth are associated with perinatal asphyxia, and to examine the relation of interleukin-6 levels to the severity of hypoxic-ischemic encephalopathy and to the neurological outcome. Serum interleukin-6 levels were measured at birth, 24 and 48 h of life in 50 consecutive term uninfected newborns with perinatal asphyxia and 113 randomly selected healthy term newborns, and at delivery in their mothers. The median cord interleukin-6 concentrations in the infants who developed hypoxic-ischemic encephalopathy was 376-fold as high as the values in the normal infants (P < 0.0001) and 5.5-fold as high as those in the infants with asphyxia who did not develop hypoxic-ischemic encephalopathy (P < 0.05). There was also a significant relationship between interleukin-6 and the degree of hypoxic-ischemic encephalopathy, and between interleukin-6 and neurodevelopmental outcome at 2 years of age. Regardless of outcome, in the asphyxiated infants the interleukin-6 values were significantly lower at both 24 and 48 h of life than at birth, with a significant decline from 24 to 48 h of life. Among mothers of the asphyxiated neonates, there were no significant differences in interleukin-6 concentrations between those delivering neonates with and without hypoxic-ischemic encephalopathy. Measurement of IL-6 concentrations in the umbilical cord of neonates with perinatal asphyxia may be useful to identify early, and in a relatively simple way, those who are most likely to have subsequent brain injury and adverse outcome.

Preemptive analgesia with epidural bupivacaine plus fentanyl in gynaecological surgery—effects on serum interleukin-6 concentrations

Abstract Purpose: The aim of this study was to evaluate preemptive analgesia and its influence on interleukin-6 (IL-6) levels. Methods: Thirty patients scheduled for hysterectomy were randomised in two groups to receive 13 ml bupivacaine 0.25% plus fentanyl (100 μg) before incision and 15 ml of saline after incision (group I, GI), or 15 ml of saline before incision and 13 ml bupivacaine 0.25% plus fentanyl (100 μg) after incision (group II, GII). General anaesthesia was performed using propofol/pancuronium/O2/isoflurane. Postoperative analgesia consisted of epidural bolus doses of 4 ml bupivacaine 0.25% plus fentanyl (50 μg) or dipyrone i.v. on demand. Pain was assessed by visual analogue scale (VAS). IL-6 levels were quantified during the study. Results: Patients in group I had significantly less pain only at arrival in recovery room. The requirements for rescue analgesia were similar in both groups and there were no significant differences in IL-6 concentrations. Conclusions: This study showed no preemptive effect of epidural fentanyl plus bupivacaine on postoperative pain and stress response as measured by IL-6 concentrations.

Increased mucosal inflammatory cytokines in children with Helicobacter pylori-associated gastritis.

The concentrations of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1-beta in tissue homogenates of gastric mucosal biopsy specimens, and in gastric juice samples from Helicobacter pylori-positive and -negative children, were determined. The study population comprised 30 children with recurrent abdominal pain attending upper gastrointestinal endoscopy. Of these patients 18 were infected with H. pylori. Cytokine concentrations in gastric biopsy homogenate supernatants and in gastric juice were measured by enzyme-linked immunosorbent assay (ELISA). TNF-alpha levels in gastric juice and in gastric biopsy homogenate supernatants in patients with H. pylori-positive gastritis were found to be significantly higher than those in children without H. pylori infection. IL-6 levels were also higher in H. pylori-infected subjects, but the difference in IL-6 concentrations measured in gastric juice and biopsy homogenate supernatants did not reach statistical significance. IL-1-beta concentrations in both specimens showed no significant difference between the two groups of children. It was suggested that increased levels of inflammatory cytokines, especially TNF-alpha and IL-6 generated locally within the gastric mucosa might be implicated in the pathogenesis of H. pylori-associated gastritis in childhood.

Maternal serum interleukin-6 concentrations in patients with preterm premature rupture of membranes and evidence of infection

OBJECTIVE: Our purpose was to determine whether maternal serum interleukin-6 concentrations are elevated in patients with preterm premature rupture of membranes and intrauterine infection. STUDY DESIGN: By use of a sensitive enzyme-linked immunosorbent assay maternal serum interleukin-6 concentrations were measured in 110 samples from patients at 22 to 34 weeks gestation with the following conditions: nonlaboring, uninfected controls (n = 46), preterm premature rupture of membranes >48 hours before delivery without infection (n = 27), preterm premature rupture of membranes 24 to 48 hours before delivery with subsequent clinical or histologic infection (n = 11), and preterm premature rupture of membranes <24 hours before delivery with infection present by clinical or histologic criteria (n = 26). The Mann-Whitney U test was used for statistical analysis. RESULTS: Compared with that of nonlaboring controls, serum interleukin-6 was significantly higher in patients with preterm premature rupture of membranes <24 hours before delivery with evidence of infection (17.2 vs 1.6 pg/ml, p < 0.0001). Patients with preterm premature rupture of membranes 24 to 48 hours before delivery who had infection had significantly higher interleukin-6 concentrations than did nonlaboring controls (3.6 vs 1.6 pg/ml, p = 0.006). There was no significant difference in interleukin-6 concentrations in nonlaboring controls compared with patients with preterm premature rupture of membranes when serum was obtained >48 hours before delivery (1.6 vs 1.6 pg/ml, p = 0.90). A serum interleukin-6 level ≥8 pg/ml yielded a sensitivity of 81%, a specificity of 99%, a positive predictive value of 96%, and a negative predictive value of 95% for identifying intrauterine infection in patients with preterm premature rupture of membranes on the day of delivery. CONCLUSIONS: Maternal serum interleukin-6 concentrations are elevated in patients with preterm premature rupture of membranes with clinical or histologic chorioamnionitis. (Am J Obstet Gynecol 1996;175:966-9.)