Blood Interleukin-6 Concentrations Research Articles

Two cases of Leukemoid reaction in premature infants caused by fetal inflammatory response syndrome

BackgroundFetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients’ hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts.Case presentationWe performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies’ alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal.Conclusions . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions.

The effect of sodium-glucose co-transporter-2 (SGLT2) inhibitors on blood interleukin-6 concentration: a systematic review and meta-analysis of randomized controlled trials

BackgroundThe low-grade chronic inflammation in diabetes plays an important role in development of cardiovascular and renal complications. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recognized as protective agents for cardio-renal complications. Interleukin-6 (IL-6) is positively associated with the pathophysiology of metabolic-related pathologies. The aim of this meta-analysis is to investigate the effect of SGLT2 inhibitors on blood IL-6 concentration in randomized controlled trials (RCTs).MethodsEmbase, PubMed, and Scopus were systematically searched up to 1st of November 2023. The eligible studies were RCTs with adult population that had provided blood IL-6 for both control and intervention groups. Cochrane risk-of-bias tool were for study quality assessment. Data were analyzed using random effect model via Stata statistical software.ResultsEighteen studies with a total of 5311 patients were included. Of which 3222 and 2052 patients were in intervention and control arm, respectively. Of the total population, 49.7% were men. The study durations ranged from 8 to 52 weeks. The pooled analysis showed a significant association between the use of SGLT2 inhibitors and lower IL-6 levels (standardized mean difference (SMD) = -1.04, Confidence Interval (CI): -1.48; -0.60, I2 = 96.93%). Dapagliflozin was observed to have a higher IL-6-lowering effect (SMD = -1.30, CI: -1.89; -0.71, I2 = 92.52) than empagliflozin or canagliflozin. Sub-group analysis of control groups (SMD = -0.58 (-1.01, -0.15) and -1.35 (-2.00, -0.70 for the placebo and active control sub-groups, respectively) and duration of interventions (SMD = -0.78 (-1.28, -0.28) and -1.20 (-1.86, -0.55) for study duration of ≤ 12 and > 12 weeks, respectively) did not change the results. Meta-regression analysis showed a significant correlation between the level of HbA1c and IL-6-lowering efficacy of SGLT2 inhibitors.ConclusionIL-6 levels are significantly reduced with the use of SGLT2 inhibitors with HbA1c as the only marker influencing such reductions, and dapagliflozin had the highest potency. The anti-inflammatory effect of SGLT2 inhibitors supports their broader use to address diabetic complications related to inflammatory responses.

Presence of Elevated Interleukin – 6 (IL-6) in the Blood of COVID-19 Convalescent Patients (40 – 93 Days) Post Onset of Symptoms Could be an Indicator of Ongoing Activation of the Immune System

IL-6 concentrations rise with the onset of COVID-19 infection and is detected in 68% of patients on admission but is expected to reduce after the acute phase. IL-6 concentrations at time points: (2-7 days), (6-11 days), (11-15 days) and (13-20 days) after intensive care unit (ICU) admission showed the highest level of IL-6 concentrations at time point 2-7 days, we decided to characterize IL-6 concentrations in serum samples collected in the sera of COVID-19 convalescent patients (40 – 93 days) post onset of symptoms. The estimated IL- 6 concentrations detected ranged between 2.65 pg/ml and 29.01 pg/ml, with a median of 9.18 pg/ml. Nine out of the 28 (32.14%) patients had normal IL-6 levels (<7 pg/ml) and 19 of the 28 patients (68%) had IL-6 elevated concentrations (>7 pg/ml). The IL-6 concentrations were grouped normal (<7 pg.ml, n= 9), mildly elevated (7 – 10 pg/ml, n = 10) and elevated (>10 pg/ml n = 9). There was no relationship between IL-6 concentrations with gender, days from onset of symptoms, days from subsiding symptoms and COVID-19 IgG antibodies. There was some relationship with age, as the younger patient cohort produced much higher IL-6 concentrations than the older patient cohort. This study describes an increase in blood IL-6 concentrations in the sera of COVID-19 convalescent patients (40 – 93 days) post onset of symptoms like that seen in COVID patients on admission and higher levels seen in the younger patient cohort indicating that “cytokine storms” still occur in the recovery phase.

Assessments of sarcopenia and its associated factors in community-dwelling middle-aged and older Chinese adults in Kelantan, Malaysia

Sarcopenia is an emerging public health problem worldwide, but very limited information exits concerning the influence of lifestyle factors and inflammation on sarcopenia among community-dwelling older populations in Asia, including Malaysia. A total of 230 apparently healthy community-dwelling middle-aged and older Chinese adults were included in the study. Validated questionnaires were used to assess dietary and lifestyle practices, while pro-inflammatory cytokine status was assessed by blood interleukin-6 concentrations (IL-6). Sarcopenia risk was assessed by the newly revised diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of sarcopenia was 12.5% with similar proportions of males and females. Multivariate logistic regression analysis showed that older age and higher concentrations of pro-inflammatory cytokine levels of IL-6 were significantly associated with a greater risk of sarcopenia, after adjustments for potential known biological and body composition factors. The present findings indicate that older adults aged 70 years and above with higher inflammation levels had a significantly increased risk of sarcopenia. Hence, effective dietary and lifestyle intervention strategies should emphasize reducing the inflammation associated with aging to prevent the rapid loss of muscle mass and strength that can lead to sarcopenia.

Heparin-Binding Protein in Bronchoalveolar Lavage Fluid as a Biomarker for Discriminating Severe Bacterial and Viral Pneumonia in Critically Ill Children.

This study is aimed at exploring the ability to use heparin-binding protein (HBP) in bronchoalveolar lavage fluid (BALF) to differentially diagnose bacterial infection from viral infection for severe community-acquired pneumonia (CAP) in critically ill children. A total of 181 children with severe CAP admitted to the intensive care unit (ICU) were included in this study. BALF and blood samples were collected within the first 24 hours of admission. BALF HBP and interleukin-6 (IL-6) concentrations and neutrophil percentage (N%) as well as blood HBP, IL-6, procalcitonin (PCT), C-reactive protein, white blood cell concentrations and N% were measured. Of the enrolled children, 126 were confirmed to have bacterial pneumonia, and 55 were confirmed to have viral pneumonia. Blood HBP and PCT concentrations and N% and BALF HBP and IL-6 concentrations and N% were significantly higher in bacterial pneumonia than in viral pneumonia (P < 0.05). In the bacterial pneumonia group, HBP and IL-6 concentrations and N% in BALF samples were all significantly higher than those in blood samples (P < 0.001), and BALF HBP and IL-6 concentrations and N% were correlated with blood HBP and IL-6 concentrations and N%, respectively (r = 0.439, 0.250, and 0.235, P < 0.01). BALF N% and blood N% were both correlated with BALF HBP concentrations and blood HBP concentrations, respectively (r = 0.622 and 0.346, P < 0.001). ROC analysis revealed that BALF HBP showed the best ability to predict bacterial pneumonia, with an area under the curve of 0.994, a sensitivity of 95.24%, and a specificity of 100.00% at its optimal cutoff value of 74.05 ng/mL. BALF HBP might be a promising biomarker for the early discrimination of bacterial infection from viral infection in critically ill children with severe CAP.

Efficacy of Scrophularia striata hydroalcoholic extract and mannan-oligosaccharide on productive performance, intestinal bacterial community, and immunity in broiler chickens after infection with Campylobacter jejuni

One of the most prevalent causes of gastrointestinal disease in humans is Campylobacter jejuni, and chickens are recognized to be the most common hosts. Scrophularia striata hydroalcoholic extract (SSE) and mannan-oligosaccharide were used in a six-week pilot-scale study to assess their effectiveness against C. jejuni. A total of 560 one-day-old male broiler chickens (Ross 308) were randomly assigned to 5 groups with 8 replicates of 14 birds each. The experimental groups were as follows: negative control (NC; untreated, and uninfected); positive control (PC; untreated, infected with C. jejuni); PC + mannan-oligosaccharide (MOS); PC + 200 mg/kg of SSE (SSE200); or PC + 400 mg/kg of SSE (SSE400). All these groups (except NC) were challenged with C. jejuni on day 15. On days 15, 24, and 42, ileal and cecal digesta samples were collected for quantification of Lactobacillus spp., C. jejuni, and Coliforms. On days 24 and 42, blood samples were also collected in order to examine serum concentrations of immunoglobulins (IgA, IgG, and IgM), interleukin-6 (IL-6), and gamma interferon (IFN-γ). The results showed that decreases in final body weight, average daily gain, feed intake, and increases in overall feed conversion ratio, mortality rate, cecal coliform counts (days 24 and 42), and blood IL-6 and IFN-γ concentrations (day 24) induced by Campylobacter infection were restored in birds fed diets MOS and SSE400 to a level that was not significantly different from the NC treatment. On days 24 and 42, the population of Coliforms in the ileum was also lower (P < 0.05) in broiler chickens fed the SSE400 diet compared to chickens fed the PC diet. Among challenged birds, those fed diets MOS and SSE400 exhibited lower (P < 0.05) ileal and cecal counts of C. jejuni (days 24 and 42), but higher (P < 0.05) serum IgG (days 24 and 42) and IgA (day 24) concentrations than the PC group. In conclusion, the SSE-supplemented diet at an inclusion level of 400 mg/kg could ameliorate the detrimental effects of Campylobacter infection in broilers, which were comparable to those of the mannan-oligosaccharide supplement.

The Effect of Habitual Fat Intake, IL6 Polymorphism, and Different Diet Strategies on Inflammation in Postmenopausal Women with Central Obesity.

The hypothesis that habitual fat intake, the IL6 genotype, the Mediterranean diet or the central European diet for 16 weeks affect biomarkers of inflammation in centrally obese postmenopausal women, was tested in a randomized controlled trial. Dietary intake was assessed using a three-day food diary. Lipid parameters were measured using a Beckman Coulter AU analyzer. Transcription of TNF and IL6 genes was analyzed in peripheral blood mononuclear cells using real-time PCR. Concentrations of tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6) were measured with ELISA. rs1800795 polymorphism of IL6 was analyzed using hydrolyzing probes. Higher energy intake from fat was associated with higher IL6 levels (p < 0.05). Significantly (p < 0.01) lower total cholesterol (T-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were observed in the GG IL6 rs1800795 genotype group. Both diets significantly (p < 0.001) decreased TNFα concentrations. Neither IL6 gene transcription levels nor blood IL6 concentrations were affected by them. Our findings confirm that habitual fat intake may affect inflammation. The rs1800795 IL6 polymorphism alone did not significantly affect body weight or body composition in aimed group, but C-allele carriers had higher levels of T-C and LDL-C. This polymorphism did not affect inflammation. Both diets may lead to a decrease in TNFα concentration.

The research of inflammatory cytokines and T cell activation in peripheral blood of opportunistic infections and death in HIV

Objective The plasma levels of interleukin 6 (IL-6), high sensitive C reactive protein (hs-CRP) and the level of T cell activation were detected in the peripheral blood inflammatory factors of acquired immunodeficiency syndrome (AIDS) patients, and the relationship with opportunistic infection and prognosis was analyzed. Methods 79 human immunodeficiency virus (HIV)-positive/aids cases from May 2014 to January 2015 in first hospital of Changsha were enrolled in the study. They were divided into three groups: HIV-infected without opportunistic infections group (n=20), HIV-infected with infections group (n=43, including HIV-infected with tuberculosis group, HIV-infected with merge fungus group. HIV combined hepatitis C), death group (n=16). Serum IL-6 and the concentration of hs-CRP were detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to test the CD3+ CD4+ cell count, the percentage of CD4+ CD38+ cell and CD8+ CD38+ cell in peripheral blood mononuclear cell (PBMC). Compare the differences among the three groups. Results The results showed that: the concentration of hs-CRP and IL-6 in peripheral blood of HIV death group was significantly higher than that in other three groups (P<0.05). The concentration of hs-CRP and IL-6 in the peripheral blood of the HIV-infected with tuberculosis group and HIV-infected with merge fungus group were significantly higher than that in the HIV-infected without opportunistic infections group (P<0.05), and the hs-CRP in the peripheral blood of the HIV combined with the hepatitis C group was higher than that in the HIV-infected without opportunistic infections group (P<0.05). The number of CD3, CD4T lymph nodes in the death group and the combined opportunistic infection group was significantly lower than that in the HIV-infected without opportunistic infections group (P<0.05). The HIV-RNA expression in peripheral blood of the death group and the combined opportunistic infection group was significantly lower than that in the HIV-infected without opportunistic infections group (P<0.05). The expression of CD8+ CD38+ on PBMC in the HIV-infected without opportunistic infections group was significantly lower than that in the death group, the tuberculosis group, the fungus group and the hepatitis C group (P<0.05). The expression of CD4+ CD38+ on PBMC in the HIV-infected without opportunistic infections group was higher than that in the death group (P< 0.05). Conclusions The concentration of inflammatory cytokines (IL-6, hs-CRP) and the expression level of T cell surface CD8+ CD38+ related to immune activation were associated with opportunistic infection and prognosis of AIDS. Key words: Acquired immunodeficiency syndrome/ME/CO/IM; Interleukin-6/ME; C-reactive protein/ME; Antigens, CD38; AIDS-related opportunistic infections; Prognosis

META-ANALYSIS OF THE RESEARCH OF IL-6 IN PERIPHERAL BLOOD OF PATIENTS WITH INFLUENZA A(H1N1)pdm09

Interleukin-6 (IL-6) is a potent proinflammatory cytokine, which level is increased in the peripheral blood in many infectious diseases, including the flu A(H1N1)pdm09, in some cases (when the excess of his development of immune cells), resulting not only to strengthen the immune system, but also to the development of a “cytokine storm” is characterized by multi-organ failure and often followed by death. To reduce errors, increase the statistical power and increase the reliability of the results according to different researchers, as well as on the results of their own research was conducted a meta-analysis (a quantitative systematic review) of IL-6 studies in peripheral blood of patients with influenza A(H1N1) pdm09. Question: to determine with a high level of confidence, whether IL-6, a marker of the severity and prognosis of the disease. Searches were carried out research work on this subject in a variety of electronic databases (Medline, EMBASE, the Cochrane Controlled Trials Register, and others), reviews, theses, magazines, conference proceedings, and others. In the process of carrying out a meta-analysis of 5 scientific papers were selected that meet the criteria for inclusion/noninclusion in the study (characteristic of scientific papers, diagnostic criteria, age of patients, comparable groups of patients, the presence of self-control, research methodology, statistical criterion and the total number of independent stu dies). Selected studies have shown sufficient uniformity (homogeneity) comparison groups. The results of the meta-analysis are presented in tables, charts and blobogramme, meta-analysis of 5 scientific papers showed that in moderate and severe influenza A(H1N1)pdm09 noted a significant increase in the concentration of IL-6 in peripheral blood of patients compared with the control a group of individuals (healthy). Severe influenza A(H1N1)pdm09 with a high probability of death is characterized by an even greater increase in IL-6 levels (in comparison with the moderate flow) — 11 pg/ml or more. Thus, the results of a meta-analysis of IL-6 with a high degree of probability is defined as a biomarker of disease severity and prognosis of development. At the same time, a result of meta-analysis of observed quite significant changes of the absolute values of the concentration of IL-6 in peripheral blood, which can be explained by using various test patterns and laboratory equipment, so that necessary to accumulate research experience level IL-6 on one and the same test systems and laboratory equipment.

Intraamniotic inflammation and umbilical cord blood interleukin-6 concentrations in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To evaluate umbilical cord blood interleukin (IL)-6 concentrations and the occurrence of fetal inflammatory response syndrome (FIRS) with respect to microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). Methods: One-hundred-eighty-eight women with singleton pregnancies complicated by PPROM between gestational ages of 24 + 0 and 36 + 6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood IL-6 concentrations were evaluated using ELISA kits. FIRS was defined as umbilical cord blood IL-6 > 11 pg/mL. Result: Women with MIAC and IAI had higher IL-6 concentrations than women without these complications (with MIAC: median 18.1 pg/mL versus without MIAC: median 5.8; p < 0.0001; with IAI: median 32.9 pg/mL, versus without IAI: median 5.8; p < 0.0001). Women with IAI with MIAC and women with IAI without MIAC had the highest umbilical cord blood IL-6 concentrations (medians: 32.6 and 39.4 pg/mL) and rates of FIRS (78% and 67%). Conclusions: IAI was associated with the highest umbilical cord blood IL-6 concentrations and rate of FIRS independent of the presence or absence of MIAC.

PROSPECTS FOR USING TOCILIZUMAB IN SYSTEMIC SCLEROSIS

Interleukin 6 (IL-6) is one of the key cytokines that are involved in inflammation and that has pleiotropic properties. Diverse effects of IL-6 result from the transmission of an intracellular signal in two ways: via direct binding to a membrane receptor having a molecular mass of 80 kDA (a classical way) or absorption of the IL-6 complex with its soluble receptor on another transmembrane receptor – gp-130 (trans-signaling). Different signaling pathways lead to various consequences. The classical way of signal transmission activates mainly protective and regenerative processes; trans-signaling has a proinflammatory potential. The review gives schemes of signal stimuli and shows that IL-6 and its receptors are a dynamic intricately organized regulatory system that can adapt to stress-induced homeostatic changes. It considers in detail evidence suggesting the effect of IL-6 on the development and maintenance of a number of systemic sclerosis (SS)-specific pathogenetic disorders, such as the activation of the endothelium, the development and maintenance of inflammation, and excessive deposition of extracellular matrix components in tissues. Endothelial cell activation during trans-signaling gives rise to an enhanced adhesion molecule expression, chemokine release, and further production of IL-6. Excessive secretion of the latter may initiate a fibrosing process and favor the further development of pathological conditions. Autoimmune disorders theoretically associated with IL-6 overproduction occur in SS. Elevated blood IL-6 concentrations in SS are related to disease clinical parameters, such as activity, severity, worse prognosis, and reduced survival. Taken together, the data presented suggest that IL-6 blocking may have a therapeutic potential in SS. The first clinical data on successfully using the IL-6 receptor antagonist tocilizumab to treat SS are given.

Simultaneous Immunoassay Analysis of Plasma IL-6 and TNF-α on a Microchip

Sandwich enzyme-linked immunosorbant assay (ELISA) using a 96-well plate is frequently employed for clinical diagnosis, but is time-and sample-consuming. To overcome these drawbacks, we performed a sandwich ELISA on a microchip. The microchip was made of cyclic olefin copolymer with 4 straight microchannels. For the construction of the sandwich ELISA for interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α), we used a piezoelectric inkjet printing system for the deposition and fixation of the 1st anti-IL-6 antibody or 1st anti-TNF-α antibody on the surface of the each microchannel. After the infusion of 2 µl of sample to the microchannel and a 20 min incubation, 2 µl of biotinylated 2nd antibody for either antigen was infused and a 10 min incubation. Then 2 µl of avidin-horseradish peroxidase was infused; and after a 5 min incubation, the substrate for peroxidase was infused, and the luminescence intensity was measured. Calibration curves were obtained between the concentration and luminescence intensity over the range of 0 to 32 pg/ml (IL-6: R2 = 0.9994, TNF-α: R2 = 0.9977), and the detection limit for each protein was 0.28 pg/ml and 0.46 pg/ml, respectively. Blood IL-6 and TNF-α concentrations of 5 subjects estimated from the microchip data were compared with results obtained by the conventional method, good correlations were observed between the methods according to linear regression analysis (IL-6: R2 = 0.9954, TNF-α: R2 = 0.9928). The reproducibility of the presented assay for the determination of the blood IL-6 and TNF-α concentration was comparable to that obtained with the 96-well plate. Simultaneous detection of blood IL-6 and TNF-α was possible by the deposition and fixation of each 1st antibody on the surface of a separate microchannel. This assay enabled us to determine simultaneously blood IL-6 and TNF-α with accuracy, satisfactory sensitivity, time saving ability, and low consumption of sample and reagents, and will be applicable to clinic diagnosis.

Thymic involution as a predictor of early-onset neonatal sepsis

Background: Diagnosis of early-onset neonatal sepsis (EONS) is often difficult because of vague clinical signs and non-specific laboratory parameters.Objective: To assess the statistical validity of thymic size estimation as a diagnostic marker of EONS compared with cord blood interleukin-6 (IL-6) concentrations.Subjects and Methods: Thirty-two neonates delivered in hospital and admitted to the neonatal unit with EONS comprised the study group. EONS was diagnosed on the basis of development of clinical signs and symptoms of sepsis within 72 hours of birth in the presence of antenatal risk factors for chorio-amnionitis and a positive blood culture. Thirty-two gestational age- and gender-matched healthy neonates served as controls. Cord blood IL-6 concentrations were estimated by ELISA. Thymic size was assessed by sonological measurement of thymic dimensions (longitudinal and transverse diameters, thymic volume and thymic index) within 24 hours of birth in the study infants and the controls. Data were analyzed by SPSS 16·0.Results: Thymic size was significantly smaller whereas cord blood IL-6 concentrations were significantly higher (P<0·001) in the sepsis group than in the controls. Sensitivity and specificity of thymic dimensions were comparable to IL-6 concentrations for diagnosing EONS. Significant correlation was noted between reduction in thymic size and a rise in IL-6 concentrations.Conclusion: Thymic involution can be used as a reliable diagnostic marker for EONS.

Cerebral blood flow velocity in early-onset neonatal sepsis and its clinical significance

Chorioamnionitis is a known risk factor for neurological damage in newborns. The present study aimed at assessing the changes in cerebral blood flow velocity (CBFV) in early-onset neonatal sepsis (EONS) and determining its predictive value as well as prognostic significance. Inborn neonates with antenatal risk factors for chorioamnionitis were followed up for development of EONS, diagnosed by presence of clinical signs along with positive blood culture and/or elevated interleukin-6 (IL-6) concentrations (≥50pg/mL) in umbilical cord blood. Comparison group was formed by asymptomatic neonates who had risk factors for chorioamnionitis but did not develop EONS and cord blood IL-6 concentrations were <50pg/mL. CBFV (resistance and pulsatility indices, peak systolic flow velocity, and vascular diameter) of internal carotid, vertebral, and middle cerebral arteries was assessed by transcranial Doppler ultrasonography within 24h of birth. The babies were kept under clinical and radiological follow-up for a minimum period of 6months. Data were analyzed by SPSS 16.0. Final study group contained 55 neonates with sepsis and 35 asymptomatic control neonates. Blood culture was positive in 27 babies of the sepsis group with a preponderance of Gram-negative bacterial isolation. Significantly lower resistance, vasodilatation, and higher blood flow were noted in all the cerebral arteries of the sepsis group. Increase in CBFV was correlated with elevated IL-6 concentrations. CBFV parameters showed significant predictive accuracy as early diagnostic markers of EONS. Among the sepsis group, 14 patients showed signs of intracranial hemorrhage during the hospital stay of which four expired and six showed signs of ventricular dilatation during follow-up. These patients had significantly higher CBFV compared to those who survived. Assessment of CBFV at early hours of birth can be adopted as an additional bedside, non-invasive investigation with immediate diagnostic and late prognostic significance.

Cord blood erythropoietin and interleukin-6 for prediction of intraventricular hemorrhage in the preterm neonate

Objective. To evaluate cord blood erythropoietin (EPO) and interleukin-6 (IL-6) levels to predict preterm infants at risk of developing intraventricular hemorrhage (IVH).Methods. Levels of umbilical cord EPO, acid–base status and IL-6 were analyzed in 116 consecutive, preterm newborns (GA at delivery: 29 [23–34 ] weeks) born to mothers who had a clinically indicated amniocentesis to rule out infection. Early-onset neonatal sepsis (EONS) was diagnosed using symptoms, hematological criteria and blood cultures.Results. IVH was diagnosed by cranial ultrasounds. The prevalence of IVH in our population was 25% (29/116). There was a direct relationship between cord blood EPO and cord blood IL-6 concentration (r = 0.225, p = 0.014), independent of GA at birth. Elevated cord blood EPO levels (r = 0.182, p = 0.016) and GA at birth (r = −0.236, p = 0.004) remained significant independent factors associated with the risk of IVH, when evaluated with stepwise logistic regression analyses. Cord blood IL-6, pH, and EONS were not associated with IVH. These relationships remained following correction for GA at birth (p = 0.027).Conclusions. Our results suggest that elevation in cord blood EPO may predict newborns at risk for IVH, independent of fetal inflammatory status. Further studies are warranted to confirm this association.

Pro–inflammatory cytokines profiles in Nigerian pregnant women infected with Plasmodium falciparum malaria

Objective To investigate the pro-inflammatory cytokines profiles in in Nigerian pregnant women infected with Plasmodium falciparum ( P. falciparum) malaria. Methods Peripheral, and placental blood samples were collected from 96 consenting volunteers comprising 76 P. falciparium infected pregnant women and 20 healthy uninfected pregnant women in Ekpoma, Nigeria, and subjected to ELISA for cytokines evaluation. Results Increased serum concentrations of interferon-gamma (IFN-γ) was observed in infected pregnant women than their uninfected counterparts [(31.2±20.9) pg/mL vs (1.8±0.9) pg/mL] and these differences were statistically significant (χ 2 = 26.18, P <0.05). The depressed levels of interleukin-12 (IL-12) seen in peripheral blood of the infected pregnant women than the uninfected women [(13.9±3.6) pg/mL vs (28.4±5.28) pg/mL] respectively was not statistically significant (χ 2 = 4.96, P >0.05). The interleukin -6 (IL-6) was significantly elevated in infected pregnant women (81.0±26.1 pg/mL) than in the uninfected pregnant women [(25.0±5.0) pg/mL] (χ 2 = 29.58, P <0.05). In all, mean cytokines concentration of IL-6, IL-12 and IFN-γ in the placental blood from infected pregnant women were (53.5±23.4) pg/mL, (8.7±6.9) pg/mL and (16.4±4.0) pg/mL, respectively. The multigravidae had a higher haemoglobin level of 10.2 g/dL and birth weight of 3 000 g than the primigrivadae with lower haemoglobin level of 7.5 g/dL and birth weight of 2 430 g. Conclusions The elevated IFN-γamong the malarous pregnant women implicates it as the major cytokine mediator in the host responses to systematic P. falciparum malaria in our locality.

Euglycemic Hyperinsulinemia in Severe Sepsis and Septic Shock

Background: Recent studies have suggested that strict glucose control with intensive insulin therapy in critically ill patients may result in better outcomes. Whether this is also true in septic shock has not been determined. In addition, whether it is the insulin administration per se or the glucose control that contributes to the beneficial effects is unclear. We raised the hypothesis that euglycemic hyperinsulinemia (EH) might improve the outcome from septic shock due to peritonitis. Materials and Methods: Fourteen anesthetized, mechanically ventilated, and hemodynamically monitored sheep received 1.5 g/kg body weight i.p. feces to induce sepsis. Ringer’s lactate and 6% hydroxyethyl starch solutions were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, the animals were randomized to either an EH group (n = 7) receiving insulin 0.25 U/ kg/h, 20% glucose (to maintain blood glucose at 40–90 mg/dl), and potassium (to maintain the potassium level at 4.0– 5.5 mmol/l) or a control group (n = 7) with no intervention. All animals were studied until their spontaneous death or for 30 h. Results: The EH group received a greater volume of 20% glucose, but blood glucose and potassium concentrations were similar in the two groups. No significant differences were found in hemodynamic variables. The circulating interleukin-6 levels increased in both groups after feces injection, but tended to be lower in the EH group (p < 0.05). The survival times were similar in the two groups (median 20.0 h in the EH group vs. 17.0 h in the control group; p = 0.73). Conclusions: In this clinically relevant sheep septic shock model, EH decreased blood interleukin-6 concentrations but did not change hemodynamics or improve the outcome.

Beneficial effects of alkaline phosphatase in septic shock

Alkaline phosphatase may decrease the harmful effects of lipopolysaccharide by detoxifying lipid A. The aim of this study was to investigate whether administration of alkaline phosphatase is beneficial in a clinically relevant septic shock model. Interventional laboratory study. University hospital animal research laboratory. Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (27.6 +/- 3.9 kg). Each animal received 1.5 g/kg body weight of feces intraperitoneally to induce sepsis. Ringer's lactate and a 6% hydroxyethyl starch solution were infused throughout the experiment to prevent hypovolemia. Two hours after feces injection, animals were randomized to alkaline phosphatase (60 units/kg intravenous bolus followed by a continuous infusion of 20 units/kg/hr for a total of 15 hrs) or no alkaline phosphatase (control group). All animals were studied until their spontaneous death or for a maximum of 30 hrs. Plasma alkaline phosphatase concentrations decreased in the control group but increased in the treatment group following alkaline phosphatase administration. In the treatment group, the Pao2/Fio2 ratio was higher (p < .05), blood interleukin-6 concentrations were lower (p < .05), and the survival time was longer (median time 23.8 vs. 17 .0 hrs, p < 0.05) than in the control group. There were no significant differences in systemic hemodynamics or diuresis. In this clinically relevant septic shock model, alkaline phosphatase administration improved gas exchange, decreased interleukin-6 concentrations, and prolonged survival time.

Interleukin‐6 in preterm premature rupture of membranes as an indicator of neonatal outcome

The aim of this study was to investigate whether the levels of interleukin-6 (IL-6) can be used as markers of adverse outcome in preterm neonates born after preterm premature rupture of membranes (PPROM). This study involved 109 preterm neonates and their mothers. The PPROM group consisted of 58 neonates who were born after PPROM, and the control group consisted of 51 neonates. IL-6 levels were measured in umbilical cord blood, maternal blood sampled during delivery and in neonatal blood taken on the fourth day of life. In the PPROM group, IL-6 concentrations in maternal blood, cord blood, and neonatal blood were significantly higher in neonates with sepsis, compared with those without sepsis (P < 0.001). Choosing 108.5 pg/ml as a cut-off concentration of IL-6 in umbilical cord blood for neonatal sepsis resulted in sensitivity 95%, specificity 100%, positive predictive value 100%, and negative predictive value 97.4%. Concerning IL-6 in maternal blood, a cut-off concentration of 81 pg/ml showed sensitivity 90%, specificity 97.4%, positive predictive value 94.7%, and negative predictive value 94.9%. Eighteen of 20 neonates with early sepsis and seven of nine neonates, who died in the PPROM group, were born of mothers with IL-6 levels above the cut-off concentration in their blood during delivery. IL-6 in umbilical cord blood was the most significant variable for predicting early onset sepsis in preterm neonates. IL-6 in maternal blood was indicative of intrauterine environmental threats and might be used to identify pregnancies where intervention would be appropriate.

Systemic Interleukin-6 Response to Colorectal Surgery Originates from the Bowel

Background: Surgical trauma evokes a systemic cytokine response which is enhanced in patients with colorectal cancer. The aim of this study was to locate the origin of the systemic cytokine response to colorectal surgery. Methods: The concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were analysed in systemic and mesenteric venous blood in 12 patients operated on with colorectal resections due to cancer or benign lesions. Immunohistochemical staining and analysis of tissue concentrations of IL-6 and TNF-α in homogenates from tumours and benign specimens were performed. Results: Mesenteric venous blood contained higher concentrations of IL-6 compared to systemic venous blood after resection, but not before. Tissue concentration of IL-6 was higher in the tumours compared to the benign specimens and immunohistochemistry revealed an abundance of IL-6 and TNF-α in malignant epithelium compared to benign mucosa. Conclusion: The higher concentration of IL-6 in venous blood from the mesenterium of the resected colonic segment compared to systemic levels, indicates that the bowel is the source of the IL-6 response to surgical trauma in colorectal surgery.