interleukin-8 and Hyperglycemia

Circulation on blood extracorporeally through plastic tubing activates several pathways including systemic inflammation and oxidative stress. These phenomena are suspected to participate to neurological and cardiovascular side effects observed in the patients under cardiopulmonary bypass (CPB). A direct relationship, in diabetic patients, between hyperglycemia and morbidity and mortality has been established. However, it is still unclear whether perioperative hyperglycemia has a direct effect on adverse events in cardiac surgery. The purpose of this study was to determine the influence of hyperglycemia on inflammation and oxidative stress in patients under CPB during cardiac surgery.. Control patients (n=17) and diabetic (type 2) patients (n=13) were included in this study. Blood samples were drawn before, during and after the CPB. Oxidative stress was evaluated in the plasma by direct and indirect approaches. Direct detection of ascorbyl radicals was assessed by electron spin resonance spectroscopy. An index: ascorbyl radical/vitamin C ratio is an indicator of the degree of oxidative stress taking place in the plasma. Oxygen radical absorbing capacity (ORAC) values were used as measurement of antioxidant capacity of the plasma. To determine inflammation profile of patients, we measure the evolution of plasma concentration of interleukin 8 (IL-8).. During cross clamping and post-CPB, the index ascorbyl radical/vitamin C is increased; the value of the index is more significant in diabetic patients. Concomitantly, ORAC values decreased in all the patients during cross clamping (p<0.05). Results concerning inflammatory index showed that IL-8 levels increased during the CPB.. In conclusion, the current study indicates that a systemic oxidative stress occurs during CPB and post-CPB periods and that in patients with type 2 diabetes mellitus, the systemic oxidative stress was increased.

Topics: Aged; Ascorbic Acid; Cardiopulmonary Bypass; Dehydroascorbic Acid; Diabetes Mellitus, Type 2; Electron Spin Resonance Spectroscopy; Female; Glycated Hemoglobin; Heart Valve Prosthesis Implantation; Humans; Hyperglycemia; Interleukin-8; Male; Middle Aged; Oxidative Stress

At the time of diagnosis, almost 80% of pancreatic cancer patients present with new-onset type 2 diabetes (T2D) or impaired glucose tolerance. T2D and pancreatic cancer are both associated with low-grade inflammation. Tumour-associated macrophages (TAMs) have a key role in cancer-related inflammation, immune escape, matrix remodelling and metastasis. In this study, the interplay between tumour cells and immune cells under the influence of different glucose levels was investigated. Human peripheral blood mononuclear cells were exposed in vitro to conditioned medium from BxPC-3 human pancreatic cancer cells, in normal (5 mM) or high (25 mM) glucose levels. Flow cytometry analyses demonstrated that tumour-derived factors stimulated differentiation of macrophages, with a mixed classical (M1-like) and alternatively activated (M2-like) phenotype polarisation (CD11c(+)CD206(+)). High-glucose conditions further enhanced the tumour-driven macrophage enrichment and associated interleukin (IL)-6 and IL-8 cytokine levels. In addition, hyperglycaemia enhanced the responsiveness of tumour-educated macrophages to lipopolysaccharide, with elevated cytokine secretion compared with normal glucose levels. Tumour-educated macrophages were found to promote pancreatic cancer cell invasion in vitro, which was significantly enhanced at high glucose. The anti-diabetic drug metformin shifted the macrophage phenotype polarisation and reduced the tumour cell invasion at normal, but not high, glucose levels. In conclusion, this study demonstrates that pancreatic cancer cells stimulate differentiation of macrophages with pro-tumour properties that are further enhanced by hyperglycaemia. These findings highlight important crosstalk between tumour cells and TAMs in the local tumour microenvironment that may contribute to disease progression in pancreatic cancer patients with hyperglycaemia and T2D.

Topics: CD11c Antigen; Cell Line, Tumor; Coculture Techniques; Diabetes Mellitus, Type 2; Female; Glucose; Humans; Hyperglycemia; Hypoglycemic Agents; Interleukin-6; Interleukin-8; Lectins, C-Type; Macrophages; Male; Mannose Receptor; Mannose-Binding Lectins; Metformin; Neoplasm Invasiveness; Pancreatic Neoplasms; Receptors, Cell Surface

Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and incident diabetes. We aimed to test possible differences in immune-mediated inflammatory parameters in newly-diagnosed hypertensives with or without 1-h post-load hyperglycemia. We enrolled 25 normotensives (NGT) and 50 hypertensives normotolerant on oral glucose tolerance test, further divided into two groups based on 1-h post-load plasma glucose: NGT 1-h ≥ 155 (n = 25) and NGT 1-h < 155 (n = 25). We measured toll-like receptor (TLR) 2, TLR4, nuclear factor kβ (NF-kβ), interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α. Hypertensives showed significantly worse metabolic and lipid profiles, and higher values of body mass ass index (BMI), creatinine, and inflammatory parameters, compared to controls. NGT 1-h ≥ 155 had a worse glycometabolic profile and higher values of TLR2 (9.4 ± 4.2 vs. 5.9 ± 2.6 MFI), TLR4 (13.1 ± 3.9 vs. 7.8 ± 2.3 MFI), NF-kβ (0.21 ± 0.07 vs. 0.14 ± 0.04), IL-1β (6.9 ± 3.4 vs. 3.2 ± 2.1 pg/mL), IL-6 (10.8 ± 2.6 vs. 4.1 ± 1.6 pg/mL), IL-8 (27.6 ± 9.3 vs. 13.3 ± 5.6 pg/mL), TNF-α (6.4 ± 2.9 vs. 3.3 ± 1.4 pg/mL), and high-sensitivity C-reactive protein (hs-CRP) (4.8 ± 1.5 vs. 2.7 ± 1.0 mg/dL) in comparison with NGT 1-h < 155. Matsuda-index and 1-h post-load glycemia were retained as major predictors of TLRs and NF-kβ. These results contribute to better characterizing cardiovascular risk in hypertensives.

Topics: Blood Glucose; C-Reactive Protein; Creatinine; Humans; Hyperglycemia; Hypertension; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Lipids; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

A central feature of diabetic wounds is the persistence of chronic inflammation, which is partly due to the prolonged presence of pro-inflammatory (M1) macrophages in diabetic wounds. Persistence of the M1 macrophage phenotype and failure to transition to the regenerative or pro-remodeling (M2) macrophage phenotype plays an indispensable role in diabetic wound impairment; however, the mechanism underlying this relationship remains unclear. Recently, microRNAs have been shown to provide an additional layer of regulation of gene expression. In particular, microRNA-21 (miR-21) is essential for an inflammatory immune response. We hypothesize that miR-21 plays a role in regulating inflammation by promoting M1 macrophage polarization and the production of reactive oxygen species (ROS). To test our hypothesis, we employed an in vivo mouse skin wound model in conjunction with an in vitro mouse model to assess miR-21 expression and macrophage polarization. First, we found that miR-21 exhibits a distinct expression pattern in each phase of healing in diabetic wounds. MiR-21 abundance was higher during early and late phases of wound repair in diabetic wounds, while it was significantly lower in the middle phase of wounding (at days 3 and 7 following wounding). In macrophage cells, M1 polarized macrophages exhibited an upregulation of miR-21, as well as the M1 and pro-inflammatory markers IL-1b, TNFa, iNos, IL-6, and IL-8. Overexpression of miR-21 in macrophage cells resulted in an upregulation of miR-21 and also increased expression of the M1 markers IL-1b, TNFa, iNos, and IL-6. Furthermore, hyperglycemia induced NOX2 expression and ROS production through the HG/miR-21/PI3K/NOX2/ROS signaling cascade. These findings provide evidence that miR-21 is involved in the regulation of inflammation. Dysregulation of miR-21 may explain the abnormal inflammation and persistent M1 macrophage polarization seen in diabetic wounds.

Topics: Animals; Diabetes Mellitus, Experimental; Female; Gene Expression Regulation; Humans; Hyperglycemia; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Macrophage Activation; Macrophages; Mice; Mice, Inbred C57BL; MicroRNAs; Middle Aged; NADPH Oxidase 2; Nitric Oxide Synthase Type II; Phosphatidylinositol 3-Kinases; Reactive Oxygen Species; Signal Transduction; Tumor Necrosis Factor-alpha; Up-Regulation; Wound Healing

Diabetes mellitus, a metabolic disease characterized by hyperglycemia and poor glucose control, is a risk factor for

Topics: Adult; Aged; Case-Control Studies; Cell Survival; Diabetes Mellitus, Type 2; Female; Gene Expression; Glucose; Humans; Hyperglycemia; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Lipoproteins; Male; Middle Aged; Monocytes; Mycobacterium tuberculosis; Primary Cell Culture; Toll-Like Receptor 2; Toll-Like Receptor 4; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha

Children with CF are insulin deficient from infancy but very little is known about the impact of glucose abnormalities in early life. We aimed to identify and describe interstitial glucose levels in CF children <6 years and to evaluate the association with pulmonary infection and inflammation.. We assessed 18 children (5 females) with median age of 3.2 years (range 0·9-5.5) with Continuous Glucose Monitoring for 3 days. Bronchoalveolar lavage (BAL) fluid was cultured for known pathogenic microbial agents and assessed for total white blood cells, percentage of neutrophils and IL-8 level.. Children with CF frequently demonstrate elevated SG levels before age 6 years, which are associated with increased pulmonary inflammation and Pseudomonas aeruginosa infection. Transient SG elevations into the diabetic range (≥11.1 mmol/L) were identified in children from 1 year of age.

Topics: Australia; Blood Glucose; Bronchoalveolar Lavage Fluid; Child, Preschool; Correlation of Data; Cystic Fibrosis; Female; Humans; Hyperglycemia; Infant; Interleukin-8; Leukocyte Count; Male; Monitoring, Physiologic; Neutrophils; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections

Hyperglycemia increases the risk of preeclampsia. Hyperglycemia induces a placental trophoblast inflammatory (IL-1β, IL-6, IL-8), antiangiogenic (sFlt-1, sEndoglin), and anti-migratory profile. The IL-1β response is mediated via inflammasome activation by the damage-associated molecular pattern (DAMP), uric acid. The objective of this study was to determine the role of high-mobility group box-1 (HMGB1), a DAMP that activates Toll-like receptor 4 (TLR4), in human first trimester trophoblast responses to hyperglycemia. The trophoblast response to excess glucose under different oxygen tensions was also investigated.. The human first trimester trophoblast cell line (Sw.71) was exposed to glucose mimicking normoglycemia (5 mmol/L) and hyperglycemia (10 mmol/L), either alone or with the TLR4 antagonist, LPS-RS; or the HMGB1 inhibitor, glycyrrhizin. Cells were also treated with glucose under hyperoxic (21% O. Excess glucose triggered a trophoblast sterile inflammatory IL-8 and antimigratory response through HMGB1 activation of TLR4. The IL-1β and sFlt-1/PlGF response was TLR4-mediated, but HMGB1-independent, suggesting another DAMP may be involved. Hyperoxia rather than normoxia or hypoxia was a major driver of trophoblast dysfunction in response to excess glucose.. The findings from this study indicate a novel mechanism by which hyperglycemia may impact trophoblast function, early placentation, and ultimately, pregnancy outcome.

Topics: Alarmins; Cell Line; Cell Movement; Female; Glycyrrhizic Acid; HMGB1 Protein; Humans; Hyperglycemia; Inflammation; Interleukin-1beta; Interleukin-8; Pre-Eclampsia; Pregnancy; Risk; Signal Transduction; Toll-Like Receptor 4; Trophoblasts; Vascular Endothelial Growth Factor Receptor-1

While diabetes and APS are individually associated with increased risk of poor perinatal outcomes, in particular preeclampsia, recent studies have demonstrated an association between concurrent aPL and diabetes leading to an increased risk of pregnancy morbidity. Hyperglycemia and aPL have independently been shown to alter human trophoblast function by inducing a pro-inflammatory, anti-angiogenic, and antimigratory response. However, little is known about the effects of concurrent hyperglycemia and aPL on trophoblast function.. A human first-trimester extravillous trophoblast cell line was exposed to glucose at 5 mmol/L (normoglycemia) or 25 mmol/L (hyperglycemia), all in the presence or absence of low-dose aPL or control IgG. For some experiments, the TLR4 antagonist, LPS-RS, was included. Cell culture supernatants were measured for inflammatory IL-1β and IL-8, and angiogenic PlGF, sFlt-1, and sEndoglin by ELISA. Inflammasome-associated uric acid was measured using a bioassay; caspase-1 was measured using an activity assay. Trophoblast migration was quantified using a two-chamber colorimetric assay.. Compared to excess glucose alone, combination excess glucose and low-dose aPL (a) further augmented trophoblast inflammatory IL-1β, inflammasome-associated uric acid and caspase-1, and pro-angiogenic PlGF; (b) dampened trophoblast inflammatory IL-8, anti-angiogenic sEndoglin, and sFlt-1; and (c) further reduced trophoblast migration.. Our findings indicate that while concurrent aPL and hyperglycemia are overall detrimental to trophoblast function, the presence of two simultaneous insults triggers some protective effects.

Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Cell Line; Cell Movement; Diabetes Mellitus; Endoglin; Female; Glucose; Humans; Hyperglycemia; Interleukin-1beta; Interleukin-8; Membrane Proteins; Pregnancy; Pregnancy Complications; Toll-Like Receptor 4; Trophoblasts; Vascular Endothelial Growth Factor Receptor-1

Diabetes is associated with chronic inflammation and activation of the vascular endothelium and the coagulation system, which in a more acute manner are also observed in sepsis. Insulin and metformin exert immune modulatory effects. In this study, we aimed to determine the association of diabetes and preadmission insulin and metformin use with sepsis outcome and host response.. We evaluated 1104 patients with sepsis, admitted to the intensive care unit and stratified according to the presence or absence of diabetes mellitus. The host response was examined by a targeted approach (by measuring 15 plasma biomarkers reflective of pathways implicated in sepsis pathogenesis) and an unbiased approach (by analyzing whole genome expression profiles in blood leukocytes).. Diabetes mellitus was not associated with differences in sepsis presentation or mortality up to 90 days after admission. Plasma biomarker measurements revealed signs of systemic inflammation, and strong endothelial and coagulation activation in patients with sepsis, none of which were altered in those with diabetes. Patients with and without diabetes mellitus, who had sepsis demonstrated similar transcriptional alterations, comprising 74 % of the expressed gene content and involving over-expression of genes associated with pro-inflammatory, anti-inflammatory, Toll-like receptor and metabolic signaling pathways and under-expression of genes associated with T cell signaling pathways. Amongst patients with diabetes mellitus and sepsis, preadmission treatment with insulin or metformin was not associated with an altered sepsis outcome or host response.. Neither diabetes mellitus nor preadmission insulin or metformin use are associated with altered disease presentation, outcome or host response in patients with sepsis requiring intensive care.

Topics: Aged; Biomarkers; Chemokine CX3CL1; Critical Illness; Diabetes Mellitus; E-Selectin; Female; Humans; Hyperglycemia; Inflammation; Insulin; Intensive Care Units; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Metformin; Middle Aged; Prospective Studies; Sepsis; Statistics, Nonparametric; Survival Analysis; Treatment Outcome; Tumor Necrosis Factor-alpha

The aim of this study is to assess the short-term effects of non-surgical periodontal therapy (NSPT) on the gingival crevicular fluid (GCF) cytokine profile in sites with standardized periodontal bony defects in beagle dogs with and without diabetes.. Four beagle dogs with streptozotocin (STZ)-induced diabetes and four healthy dogs were included. Fasting blood glucose levels were measured using a glucometer. In all animals, a 3-walled bony defect was created on the mesial surface of the second premolar and first molar in all quadrants. After 12 weeks, all animals underwent weekly NSPT for 3 weeks. Baseline and post-NSPT GCF samples were collected, and levels of interleukin (IL)-1, IL-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay. Statistical analyses were performed using a software program, and P values <0.05 were considered statistically significant.. Mean fasting blood glucose levels were significantly higher in dogs with induced diabetes than those without diabetes (P <0.01). At baseline, mean IL-6 (P <0.01) and IL-8 (P <0.05) levels were higher in dogs with diabetes than those without diabetes. A significant reduction in levels of IL-1, IL-1β, IL-6, IL-8, and TNF-α was noted in dogs without diabetes 1 week after NSPT. However, this significant reduction (P <0.05) only appeared 2 weeks after NSPT in dogs with diabetes.. NSPT reduces GCF levels of proinflammatory cytokines in dogs with and without STZ-induced diabetes; however, chronic hyperglycemia seems to retard the effect of NSPT on GCF cytokine concentration.

Topics: Alveolar Bone Loss; Animals; Blood Glucose; Cytokines; Diabetes Mellitus, Experimental; Dogs; Fasting; Gingival Crevicular Fluid; Hyperglycemia; Interleukin-1; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Periodontal Debridement; Periodontal Index; Periodontal Pocket; Streptozocin; Time Factors; Tumor Necrosis Factor-alpha

Acute hyperglycemia is considered as a pro-inflammatory state and is related to an adverse outcome in critically ill adults. Neonates are susceptible to infections and systemic inflammatory response syndrome induced by pro-inflammatory cytokines. This study focuses on the interaction between neonatal glucose homeostasis and the pro-inflammatory cytokine production in term and preterm infants in-vitro.. We analyzed the pro-inflammatory cytokine production in whole cord blood of term infants (n = 10), preterm infants > 32 weeks (n=16) and preterm infants ≤32 weeks of gestational age (n = 13) and in adult controls (n=14) using an in-vitro sepsis-model. Whole blood was pre-incubated with different concentrations of glucose (0-1000 mg/dl) and insulin (0-62.5 IE/l) and stimulated with lipopolysaccharide. The intracytoplasmatic TNF-α, IL-6, and IL-8 response was measured by flow cytometry.. In-vitro hyperglycemia induced a dose-dependent increase of IL-8 in all age groups while TNF-α was demonstrated to be stimulated by glucose in cord blood samples of preterm infants ≤32 weeks of gestational age and term infants. In contrast, insulin showed no significant effects on pro-inflammatory cytokine production in-vitro.. Acute hyperglycemia may induce pro-inflammatory cytokine responses in neonatal whole blood in-vitro. These data provide a basis for further in-vitro signal transduction studies and in-vivo investigations about the significance of neonatal glucose homeostasis and its impact on long-term outcome of this susceptible patient cohort.

Topics: Cytokines; Fetal Blood; Gestational Age; Glucose; Humans; Hyperglycemia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Insulin; Interleukin-6; Interleukin-8; Lipopolysaccharides; Models, Biological; Sepsis; Tumor Necrosis Factor-alpha

Endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) have been implicated in a number of complications associated with diabetes mellitus including micro- and macrovascular dysfunction. In this study we examine ER stress levels in blood cells isolated from human subjects with metabolic syndrome and in healthy controls. Total RNA and protein were isolated from leukocytes and the levels of specific ER stress markers were quantified by real-time-PCR and immunoblot analysis. Our results indicate that, compared to healthy controls, individuals with metabolic syndrome have elevated mRNA levels of genes indicative of ER stress; including spliced XBP-1 (sXBP-1), Grp78, and CHOP. Induced ER stress levels correlate with blood glucose but not plasma lipid concentration. Furthermore, in healthy individuals, a standard 75 g oral glucose challenge produced a significant elevation in spliced XBP-1 (1.3 fold), Grp78 (2.0 fold), and calreticulin (3.5 fold) mRNA 60 min post challenge and a significant increase in Grp78 (2.0 fold), calreticulin (2.7 fold) protein levels 2 h postchallenge, relative to fasting levels. The UPR was also activated ex vivo, in human leukocytes cultured in the presence of 15 mmol/l glucose, supporting a specific role for glucose. The oral glucose challenge was associated with a significant increase in the expression of inflammatory cytokines, including interleukin (IL)-1α/β, IL-6, and IL-8, that may result from ER stress. These findings suggest that there is an association between both acute and chronic dysglycemia and ER stress in humans.

Topics: Acute Disease; Adult; Calreticulin; Case-Control Studies; DNA-Binding Proteins; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Female; Glucose Tolerance Test; Heat-Shock Proteins; Humans; Hyperglycemia; Immunoblotting; Interleukin-1; Interleukin-6; Interleukin-8; Male; Metabolic Syndrome; Monocytes; Real-Time Polymerase Chain Reaction; Regulatory Factor X Transcription Factors; RNA, Messenger; Signal Transduction; Transcription Factor CHOP; Transcription Factors; Unfolded Protein Response; X-Box Binding Protein 1

We investigated C-peptide effects on inflammatory cytokine release and adhesion of monocytes exposed to high glucose and lipopolysaccharide (LPS) in vitro.. Monocytic cells (U-937) were cultured in the presence of 30 mmol/L glucose and stimulated with 0.5 ng/μL LPS in the presence or absence of C-peptide (1 μmol/L) for 24 h to induce inflammatory cytokine secretion. Adhesion of U-937 monocytes to human aortic endothelial cells (HAEC) was also studied in the presence or absence of C-peptide. Concentrations of IL-6, IL-8, macrophage inflammatory protein(MIP)-1α, and MIP-1β in supernatants from LPS-stimulated U-937 monocytes were assessed by Luminex. To gain insights into potential intracellular signaling pathways affected by C-peptide, we investigated nuclear translocation of nuclear factor(NF)-κB p65/p50 subunits by western blot in LPS-treated U-937 cells. The effect of C-peptide on LPS-induced phosphorylation of the cytoplasmic protein IκB-α was also investigated by immunoblotting.. Addition of C-peptide significantly reduced cytokine secretion from LPS-stimulated U-937 monocytes. Adhesion of U-937 cells to HAEC was also significantly reduced by C-peptide. These effects were accompanied by reduced NF-κB p65/p50 nuclear translocation and decreased phosphorylation of IκB-α.. We conclude that, in conditions of hyperglycemia, C-peptide reduces monocytes activation via inhibition of the NF-κB pathway.

Topics: Aorta; C-Peptide; Chemokine CCL3; Chemokine CCL4; Endothelial Cells; Humans; Hyperglycemia; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharides; Monocytes; Phosphorylation; U937 Cells

Since mediators of inflammation are associated with insulin resistance, and the risk of developing diabetes mellitus and gestational diabetes, we hypothesized that genetic variation in members of the inflammatory gene pathway impact glucose levels and related phenotypes in pregnancy. We evaluated this hypothesis by testing for association between genetic variants in 31 inflammatory pathway genes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort, a large multiethnic multicenter study designed to address the impact of glycemia less than overt diabetes on pregnancy outcome.. Fasting, 1-hour, and 2-hour glucose, fasting and 1-hour C-peptide, and HbA1c levels were measured in blood samples obtained from HAPO participants during an oral glucose tolerance test at 24-32 weeks gestation. We tested for association between 458 SNPs mapping to 31 genes in the inflammatory pathway and metabolic phenotypes in 3836 European ancestry and 1713 Thai pregnant women. The strongest evidence for association was observed with TNF alpha and HbA1c (rs1052248; 0.04% increase per allele C; p-value = 4.4×10(-5)), RETN and fasting plasma glucose (rs1423096; 0.7 mg/dl decrease per allele A; p-value = 1.1×10(-4)), IL8 and 1 hr plasma glucose (rs2886920; 2.6 mg/dl decrease per allele T; p-value = 1.3×10(-4)), ADIPOR2 and fasting C-peptide (rs2041139; 0.55 ug/L decrease per allele A; p-value = 1.4×10(-4)), LEPR and 1-hour C-peptide (rs1171278; 0.62 ug/L decrease per allele T; p-value = 2.4×10(-4)), and IL6 and 1-hour plasma glucose (rs6954897; -2.29 mg/dl decrease per allele G, p-value = 4.3×10(-4)).. Based on the genes surveyed in this study the inflammatory pathway is unlikely to have a strong impact on maternal metabolic phenotypes in pregnancy although variation in individual members of the pathway (e.g. RETN, IL8, ADIPOR2, LEPR, IL6, and TNF alpha,) may contribute to metabolic phenotypes in pregnant women.

Topics: Asian People; Blood Glucose; C-Peptide; Cohort Studies; Fasting; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Inflammation; Interleukin-6; Interleukin-8; Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Receptors, Adiponectin; Receptors, Leptin; Resistin; Signal Transduction; Thailand; Tumor Necrosis Factor-alpha; White People

This study was designed to investigate the association between inflammatory cytokines (IL-8, IL-6) and IGF-1 levels in relation to metabolic control, microvascular complications and bone mineral density (BMD) in a cohort of Egyptian adolescents with T1DM.. Sixty patients with T1DM (mean age was 14.67±1.53 years, mean disease duration was 6.87±1.25 years) and 40 controls participated in the study. Thirty-six patients (60%) had poor glycemic control (HbA1C measurements ≥8%) while the rest (n=24%, 40%) had good glycemic control (HbA1C measurements <8%). Serum IL-6, IL-8, and IGF-1 levels were measured. Whole body DXA scan were assessed. Total body and lumbar spine (L2-L4) bone mineral content (BMC, g) and bone area (BA, cm(2)) were measured by DXA scan, bone mineral density (BMD, g/cm(2)) was calculated by BMC/BA.. Patients with T1DM had higher IL-6 and IL-8 levels with lower IGF-1 than healthy controls (P<0.001). Within the T1DM patients those with poor glycemic control had higher IL-6 and IL-8 as well as lower IGF-1 and total BMD than those with good glycemic control (P<0.001 for all). IL-6 and IL-8 were negatively correlated with IGF-1 (P=0.005 and 0.021, respectively). The peripheral neuropathy rate was also greater in T1DM patients with poor glycemic control (P=0.02). Presence of nephropathy or retinopathy was not different (P=0.69 and 0.50, respectively).. High IL-6, IL-8 with low IGF-1 levels are found in adolescents with T1DM. It seems that poor glycemic control exacerbates inflammatory cytokines, increases peripheral neuropathy, and decreases bone mineral density.

Topics: Adolescent; Biomarkers; Bone Density; Case-Control Studies; Diabetes Mellitus, Type 1; Female; Humans; Hyperglycemia; Inflammation Mediators; Insulin-Like Growth Factor I; Interleukin-6; Interleukin-8; Male; Microvessels

Impaired wound healing is a major complication associated with diabetes, involving a dysregulation and impairments in the inflammatory and angiogenic phases of wound healing. Here, we examine the effects of the neuropeptides substance P (SP) and neuropeptide Y (NPY) on dermal microvascular endothelial cell (DMVEC) angiogenesis and interleukin-8 (IL-8) expression, a known effector of the neuropeptide pathways in normal and hyperglycemic conditions in vitro.. DMVECs are treated with one of four glucose concentrations: 1) 5 mM glucose; 2) 10 mM glucose; 3) 30 mM glucose; or 4) 30 mM mannitol and cotreated with 100 nM NPY, 100 nM SP, or 10 ng/mL IL-8. Angiogenesis is assessed with proliferation and tube formation assays. IL-8 mRNA and protein expression are evaluated at days 1 and 7.. As compared with noromoglycemia (5 mM glucose), hyperglycemia (30 mM glucose) decreases DMVEC proliferation and tube formation by 39% and 42%, respectively. SP cotreatment restores DMVEC proliferation (211%) and tube formation (152%), and decreases IL-8 expression (34%) in DMVECs exposed to hyperglycemic conditions. These effects are not observed with NPY. However, IL-8 treatment by itself does not affect proliferation or tube formation, suggesting that the effect of SP on DMVEC angiogenesis is unlikely through changes in IL-8 expression.. Hyperglycemic conditions impair DMVEC proliferation and tube formation. SP mitigates the effect of hyperglycemia on DMVECs by increasing DMVEC proliferation and tube formation. These findings are not likely to be related to a dysregulation of IL-8 due to the lack of effects of hyperglycemia on IL-8 expression and the lack of effect of IL-8 on DMVEC proliferation and tube formation. The effect of SP on DMVECs makes SP a promising potential target for therapy in impaired wound healing in diabetes, but the exact mechanism remains unknown.

Topics: Cell Proliferation; Cells, Cultured; Dermis; Endothelial Cells; Endothelium, Vascular; Humans; Hyperglycemia; Interleukin-8; Microvessels; Neovascularization, Physiologic; Neuropeptide Y; Neuropeptides; Substance P; Wound Healing

The purpose of this study was to determine the inhibitory activity of trans-resveratrol against hyperglycemia-induced inflammation and degradation of gap junction intercellular communication in retinal pigment epithelial cells. Retinal (ARPE-19) cells were incubated with 5.5 mM glucose, 5.5 mM glucose and 10 microM resveratrol, 33 mM glucose, or 33 mM glucose and 0-10 microM trans-resveratrol at 37 degrees C and 5% CO(2) for 9 days. Cell viability was determined by the crystal violet assay. The levels of low-grade inflammation biomarkers interleukin-6 and interleukin-8 (IL-6 and IL-8), angiogenic factors, and vascular endothelial growth factor (VEGF) were determined by the enzyme-linked immunosorbent assay (ELISA). Gap junction intercellular communication (GJIC) was determined by the scrape-load/dye transfer method. The expression levels of protein kinase Cbeta (PKCbeta), connexin 43 (Cx43), transforming growth factor-beta1 (TGF-beta1), and cyclooxygenase-2 (COX-2) were determined by Western blot. Incubation of retinal cells with 10 microM trans-resveratrol in the presence of 5.5 mM glucose did not affect any of the biomarkers investigated. Incubation of ARPE-19 cells with 33 mM glucose for 9 days significantly induced the accumulation of VEGF, IL-6, IL-8, TGF-beta, and COX-2, activation of PKCbeta, and reduction of Cx43 and GJIC. Incubation of ARPE-19 cells with 33 mM glucose in the presence of 0-10 microM trans-resveratrol dose-dependently inhibited VEGF, TGF-beta1, COX-2, IL-6, and IL-8 accumulation, PKCbeta activation, and Cx43 degradation and enhanced GJIC. These data suggest that trans-resveratrol can protect the retinal pigment epithelial cells against hyperglycemia-induced low-grade inflammation and GJIC degradation.

Topics: Cell Line; Connexin 43; Diabetic Retinopathy; Down-Regulation; Gap Junctions; Humans; Hyperglycemia; Interleukin-6; Interleukin-8; Resveratrol; Retinal Pigment Epithelium; Stilbenes; Transforming Growth Factor beta1

Hyperglycemia and insulin resistance are common in many critically ill patients. Hyperglycemia increases the production of reactive oxygen species in cells, stimulates the production of the potent proinflammatory cytokines IL-8 and TNF-alpha, and enhances the expression of haem oxygenase-1, an inducible stress protein. It has been shown that administration of insulin and the semi-essential amino acid glutamine have been beneficial to the septic patient. The aim of our study is to test whether these two molecules, glutamine and insulin used in combination attenuate the proinflammatory responses in endothelial cells which have been triggered by hyperglycaemia. Our results demonstrate that a combination of insulin and glutamine are significantly more effective in reducing the expression of IL-8, TNF-alpha and HO-1 than insulin or glutamine alone.

Topics: Cells, Cultured; Drug Therapy, Combination; Endothelium, Vascular; Glutamine; Heme Oxygenase-1; Humans; Hyperglycemia; Hypoglycemic Agents; Inflammation; Insulin; Interleukin-8; Models, Biological; Oxidative Stress; Tumor Necrosis Factor-alpha

This study evaluated the changes in chemokine interleukin (IL)-8 production from endothelial cells under various hyperglycemic conditions and investigated whether the hyperglycemia associated with the acute inflammatory response could enhance the IL-8 production from the endothelial cells.. Human umbilical endothelial cells (HUVECs) were seeded at a concentration of 1 x 10(5) cells/well and cultured. The culture medium was replaced with Medium 199 containing various concentrations of glucose (final glucose concentration of culture medium was 100, 200, 300, 400, 500 mg/dL; n = 7 each) with or without 100 ng of tumor necrosis factor-alpha (TNF-alpha). After 12 or 24 h at 37 degrees C, the supernatants were collected from the cultures and stored at -80 degrees C until cytokine assay. IL-8 levels of the samples from the supernatants were quantified using a commercially available enzyme-linked immunosorbent assay kit.. The IL-8 production by the HUVECs was significantly higher in the high glucose culture than in the control culture (glucose concentration of 100 mg/dL) (P < 0.05). Moreover, the hyperglycemia associated with elevated TNF-alpha was found to enhance the level of IL-8 production by the HUVECs cultured at all glucose concentrations and over both time courses, compared to the control (P < 0.05).. In this study we observed a significant augmentation of IL-8 production by endothelial cells during short-term hyperglycemia, and a similar but significantly stronger augmentation was obtained through TNF treatment. These findings suggest that the hyperglycemia associated with acute inflammatory response after trauma may put the patients at high risk for secondary tissue damage.

Topics: Cells, Cultured; Culture Media; Endothelial Cells; Glucose; Humans; Hyperglycemia; Interleukin-8; Osmolar Concentration; Time Factors; Tumor Necrosis Factor-alpha; Umbilical Veins; Vasculitis

This study assessed whether hyperglycemia and lipopolysaccharide (LPS) decrease the depression effect of interleukin (IL) 8 production by hypothermia in endothelial cells.. Laboratory study in a university laboratory.. Human umbilical vein endothelial cells (HUVECs).. HUVECs were cultivated in various concentrations of glucose (5.5 or 16.5mM = 100 or 300mg/dl) with or without LPS stimulation for 5, 12, or 24h at either 30 degrees or 37 degrees C.. After culturing, IL-8 mRNA expressions and IL-8 levels were measured. At 37 degrees C, hyperglycemia significantly increased basal IL-8 mRNA at 12h and basal IL-8 at 24h. At 37 degrees C hyperglycemia significantly increased LPS-stimulated IL-8 mRNA at 12h and LPS-stimulated IL-8 at 12 and 24h. At 30 degrees C basal IL-8mRNA, basal IL-8, and LPS-stimulated IL-8 were significantly decreased by hypothermia, but these hypothermic effects were not observed in LPS-stimulated IL-8 mRNA. Furthermore even at 30 degrees C hyperglycemia significantly increased LPS-stimulated IL-8 mRNA at all time points and LPS stimulated IL-8 at 24h.. Hypothermia (30 degrees C) decreases the production of IL-8 in HUVECs but does not decrease the expression of IL-8 mRNA. When hypothermia is followed by hyperglycemia and LPS stimulation, such a combination may expose the patients to a high risk of secondary tissue damage during therapeutic hypothermia.

Topics: Endothelial Cells; Gene Expression; Humans; Hyperglycemia; Hypothermia; Interleukin-8; Lipopolysaccharides; Umbilical Veins

Elevated glucose concentrations have profound effects on cell function. We hypothesized that incubation of human aortic endothelial cells (HAEC) with high glucose increases insulin signaling and develops the appearance of insulin-stimulated glucose uptake by the cells. Compared with 5 mM glucose, incubation of HAEC with 30 mM glucose for up to 48 h increased in a time-dependent manner expression of insulin receptor, insulin receptor substrate (IRS)-1, IRS-2, and GLUT1 proteins. High glucose also increased the specific binding of (125)I-labeled insulin in HAEC accompanied by accelerated production of interleukin (IL)-6 and IL-8. Short-term stimulation by 50 microU/ml insulin did not activate [(14)C]glucose uptake by HAEC incubated in 5 mM glucose. However, an addition of insulin to high glucose-exposed endothelial cells led to a significant increase in [(14)C]glucose uptake in a glucose concentration- and time-dependent fashion, reaching a plateau at 48 h of incubation. Furthermore, incubation of HAEC with 30 mM glucose resulted in a new insulin-stimulated extracellular signal-regulated kinase-1/2 mitogen-activated protein kinase phosphorylation and increased lipid peroxidation and production of reactive oxygen species. These studies show for the first time that high glucose increases expression of insulin receptors and downstream elements of the insulin-signaling pathway and transforms "insulin-resistant" aortic endothelial cells into "insulin-sensitive" tissue regarding glucose uptake.

Topics: Aorta; Blotting, Western; Endothelial Cells; Glucose; Glucose Transporter Type 1; Humans; Hyperglycemia; Insulin; Insulin Receptor Substrate Proteins; Interleukin-6; Interleukin-8; Mitogen-Activated Protein Kinases; Phosphoproteins; Proto-Oncogene Proteins c-akt; Receptor, Insulin; Signal Transduction; Tumor Necrosis Factor-alpha

Chronic hyperglycemia is an established risk factor for endothelial damage. It remains unclear, however, whether brief hyperglycemic episodes after acute stress alter the function of vascular endothelial cells in response to endotoxin. We hypothesize that brief hyperglycemic episodes enhance the production of interleukin-8 (IL-8) after lipopolysaccharide (LPS) stimulation.. Human umbilical vein endothelial cells (HUVECs; 1 x 10(5) cells/mL, cells from subcultures 2-5, n = 6) were cultivated in various concentrations of glucose (200, 300, 400, and 500 mg/dL) with or without LPS stimulation (1 microg/mL) for 24 hours. After culture, IL-8 levels in the supernatant were measured using ELISA.. HUVECs cultured at glucose concentrations of 300 and 400 mg/dL produced more (p < 0.01) IL-8 than control cells (200 mg/dL). HUVECs cultured at glucose concentrations of 300 and 400 mg/dL also produced more (p < 0.01) IL-8 than those cultured in the absence of LPS.. Hyperglycemic conditions enhance IL-8 production by vascular endothelial cells, and this response is augmented by LPS. Infections may foster neutrophil accumulation at injury sites. These results suggest that it is important to manage even short-term increases in blood glucose after acute stress.

Topics: Cells, Cultured; Chemokines; Endothelial Cells; Humans; Hyperglycemia; Interleukin-8; Lipopolysaccharides

This study investigated the heme oxygenase-1 (HO-1) and the endotoxin-induced uveitis (EIU) in diabetic streptozotocin (STZ)-hyperglycemic rats. STZ-hyperglycemic rats had impaired levels of the enzyme HO-1 within the ciliary bodies if compared with the nondiabetic rats. STZ-hyperglycemic rats also predisposed the eye to produce high levels of both the cytokines IL-1beta and CXCL8. Subsequent EIU further and significantly (P < .01) increased the cytokines production, an effect partly prevented by hemin treatment. Most importantly, hemin, an inducer of heme oxygenase expression and activity, recovered the huge number of infiltrated polymorphonuclear leukocytes PMN within the ciliary bodies associated with STZ-hyperglycemic state and EIU damage. Impairment of the stress-sensitive enzyme HO-1 in STZ-hyperglycemic rats increases and prolongs the inflammatory response to EIU.

Topics: Animals; Ciliary Body; Diabetes Mellitus, Experimental; Enzyme-Linked Immunosorbent Assay; Heme Oxygenase-1; Hemin; Hyperglycemia; Inflammation; Interleukin-1beta; Interleukin-8; Lipopolysaccharides; Male; Neutrophils; Random Allocation; Rats; Rats, Sprague-Dawley; Streptozocin; Uveitis

The aim of the study was to investigate the association between admission blood glucose concentrations and immune function variables and its correlation to mortality rate in patients of a medical intensive care unit.. Prospective, observational study.. Medical intensive care unit of a university hospital.. Patients were 189 consecutive critically ill patients in the medical intensive care unit.. At admission to the intensive care unit, serum concentrations of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-alpha were measured with immunometric assays. Additionally, ex vivo secretion of tumor necrosis factor-alpha after stimulation with lipopolysaccharide in a whole blood assay and cytometric human leukocyte antigen-DR expression on monocytes were determined in all study subjects. Simplified Acute Physiology Score II and Therapeutic Intervention Scoring System-28 were calculated for the first day in the intensive care unit.. The relationships between blood glucose concentrations and immunologic variables were analyzed using univariate and multivariate statistical methods. Overall, 75 patients (39.7%) presented with hyperglycemia. An elevated blood glucose concentration at admission was related to an increased risk of mortality in the intensive care unit (odds ratio, 2.6; p = .009). At univariate and multivariate analysis, hyperglycemia was associated with increased serum concentrations of interleukin-6 (p < .05), a reduced ex vivo production of tumor necrosis factor-alpha (p < .01), and a history of diabetes mellitus (p < .05), whereas other clinical (including Simplified Acute Physiology Score II and Therapeutic Intervention Scoring System-28) and immunologic variables were not statistically related to blood glucose.. Our main findings show that admission hyperglycemia is statistically related to distinct changes of humoral and cellular immune functions. Furthermore, elevated glucose concentrations at admission are associated with increased intensive care unit mortality rate in a medical intensive care unit. Although these data do not explain cause and effect, our results provide a strong rationale for studying the immunologic effects of strict glycemic control in the intensive care unit during the course of critical illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; APACHE; Blood Glucose; Female; Flow Cytometry; HLA-DR Antigens; Hospital Mortality; Hospitals, University; Humans; Hyperglycemia; Intensive Care Units; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Monocytes; Patient Admission; Prognosis; Prospective Studies; Risk Factors; Survival Analysis; Tumor Necrosis Factor-alpha

Adipokines such as Plasminogen activator inhibitor-1 (PAI-1), interleukin (IL)-8, and tumor necrosis factor (TNF)-alpha are elevated in patients with obesity, insulin resistance, and type 2 diabetes. In the present study, we investigated whether glucose affected the production of these adipokines in human adipose tissue in vitro. Glucose (up to 35mM) increased secretion of PAI-1 (p<0.01) and IL-8 (p<0.01), but not TNF-alpha, in a dose- and time-dependent manner. Half-maximal stimulatory concentration of glucose was about 1mM. Glucosamine (5mM) decreased production of PAI-1 (p<0.05) and IL-8 (p<0.05), indicating that the hexosamine biosynthesis pathway is not involved in the glucose-induced increment in adipokine secretion. The present data demonstrate that glucose increases PAI-1 and IL-8 secretion. However, glucose concentrations above 5mM had no additional effects on adipokine secretion, suggesting that mechanisms other than diabetes/insulin resistance-related hyperglycemia may be involved in the observed elevation of these adipokines.

Topics: Adipose Tissue; Adult; Chemokines; Dose-Response Relationship, Drug; Female; Glucosamine; Glucose; Humans; Hyperglycemia; In Vitro Techniques; Insulin; Interleukin-8; Plasminogen Activator Inhibitor 1; RNA, Messenger; Time Factors; Tumor Necrosis Factor-alpha

Hyperglycaemia, in insulin-dependent or independent diabetes mellitus, promotes endothelial cell (EC) dysfunction and is a major factor in the development of macro- or microvascular diseases. The mechanisms and the disease-related genes in vascular diseases resulting from hyperglycaemia are poorly understood. Macroarrays. bearing a total of 588 cDNA known genes, were used to analyze HUVEC gene transcription subjected to 25 or 5-mM glucose for 24 h. Isolated mRNA derived from treated first passage HUVEC were reverse transcribed, 32P labeled, and hybridized to the cDNA macroarrays. Results show that acute hyperglycaemia induces an up-regulation of seven major genes, four of which were not previously reported in the literature. Northern blot analyses, performed on these 4 genes, confirm macroarrays results for alphav, beta4, c-myc, and MUC18. Moreover, time course analysis (0, 2, 4, 8, 2, 16, 24 h) of alphav, beta4 c-myc, and MUC18 mRNA expression, observed by northern blot assays, showed a peak at time points situated between 2 to 8 h. The 3 other genes (ICAM-1, beta1, and IL-8), were shown by others to be significantly upregulated after glucose stimulation. Furthermore, ELISA assays performed on the supernatant of HUVEC culture medium showed a significant increase of IL-8 for cells treated with 25-mM compared to 5-mM glucose. Identified genes, upregulated in endothelial cells as a result of acute hyperglycaemia, may serve as therapeutic or diagnostic targets in vascular lesions present in diabetic patients. These results also demonstrate the use of cDNA macroarrays as an effective approach in identifying genes implicated in a diseased cell.

Topics: Acute Disease; Antigens, CD; Antigens, Surface; CD146 Antigen; Cells, Cultured; Chemokine CCL2; DNA, Complementary; Endothelium, Vascular; Gene Expression Regulation; Genes, myc; Glucose; Humans; Hyperglycemia; Integrin alphaV; Integrin beta1; Integrin beta4; Intercellular Adhesion Molecule-1; Interleukin-8; Membrane Glycoproteins; Neural Cell Adhesion Molecules; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-myc; RNA, Messenger

To establish and monitor a rabbit model of graded severity of acute pancreatitis to test the hypothesis that interleukin-8 (IL-8) and the adhesion molecule complex CD11b/CD18 are involved in the development of systemic complications in severe acute pancreatitis.. Acute pancreatitis induction in rabbits by duct ligation with or without infusion of 5.0% or 0.5% chenodeoxycholic acid or 0.9% saline. Control animals underwent laparotomy. The animals were monitored biochemically, histologically and immunohistochemically.. Increased serum levels of IL-8, tumour necrosis factor alpha (TNF-alpha), amylase and lipase were found in the chenodeoxycholic acid groups when compared with the saline, duct-ligated or control groups. Leukopenia, hypocalcaemia, and hyperglycaemia were marked in the 5.0% chenodeoxycholic acid group as compared to the saline, duct-ligated and control groups. Histologically, the 5.0% chenodeoxycholic acid group manifested a significant degree of pancreatic necrosis and neutrophil infiltration. The lungs of these animals showed acute lung injury and a significant up-regulation of CD11b/CD18. IL-8 was produced in pancreatic acinar and ductal cells. A significantly large output of ascitic fluid was seen in the 5.0% chenodeoxycholic acid group.. The rabbit models of acute pancreatitis are reliable in that enzymatic and histological evidence of acute pancreatitis with or without systemic complications developed. IL-8 is produced locally in pancreatic acinar and ductal cells and significantly increased in peripheral blood during severe but not mild pancreatitis. The expression of the adhesion molecule complex CD11b/CB18 is significantly increased in lung tissue during severe acute pancreatitis with acute lung injury. IL-8 and CD11b/CB18 are involved in the pathogenesis of severe acute pancreatitis but not of mild oedematous pancreatitis.

Topics: Acute Disease; Amylases; Animals; Ascites; CD11 Antigens; CD18 Antigens; Chenodeoxycholic Acid; Cholagogues and Choleretics; Disease Models, Animal; Hyperglycemia; Hypocalcemia; Interleukin-8; Laparotomy; Leukopenia; Ligation; Lipase; Necrosis; Neutrophils; Pancreas; Pancreatic Ducts; Pancreatitis; Rabbits; Respiratory Distress Syndrome; Sodium Chloride; Tumor Necrosis Factor-alpha; Up-Regulation

As our previous studies had shown that human neutrophils could kill Rhizopus oryzae hyphae in vitro, interactions of these hyphae with neutrophils and serum were further explored. Heated or fresh normal human sera suppressed hyphal metabolic activity as determined by [14C]uracil uptake, but severe ketoacidosis (8 X 10(-3) M beta-hydroxybutyric acid plus 2 X 10(-3) M acetoacetic acid at pH 7.0) negated this effect. Hyperglycemia (500 mg/dl) and severe ketoacidosis did not affect damage to hyphae by human neutrophils. Hyphae generated factors from sera which induced comparable chemotactic responses by neutrophils obtained from both normal and diabetic subjects, using a leading front assay performed in modified Boyden chambers. Zymosan-stimulated neutrophil chemotaxis was marginally depressed only by the combined elevation of both glucose (500 mg/dl) and ketoacids (10(-2)M) irrespective of pH (7.0 to 7.4), but not by any of these factors alone. Protein-containing supernatants from live or killed hyphae were chemotactic in the absence of serum based upon "checkerboard" assays varying the concentrations of hyphal supernatants above and below filters in the Boyden chambers. The supernatant-induced chemotactic response by neutrophils from diabetic subjects was minimally less than that of normal neutrophils (P less than 0.05). These findings indicate that R. oryzae hyphae can generate chemotactic factors which might prove to influence the inflammatory response to infections in vivo, and that severe hyperglycemia and ketoacidosis might affect interaction between the host and invading hyphae in mucormycosis.

Topics: Chemotactic Factors; Chemotaxis, Leukocyte; Complement Pathway, Alternative; Diabetic Ketoacidosis; Humans; Hydrogen-Ion Concentration; Hyperglycemia; Interleukin-8; Neutrophils; Rhizopus