interleukin-8 and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

The immunomodulatory activities of recombinant human interleukin-11 (rhIL-11) were investigated in a clinical trial among patients with hematological malignancy, randomized to either rhIL-11 or placebo throughout chemotherapy. Daily serum concentrations of sTNFRI, IL-6, IL-8, TNFalpha, and CRP were measured. Higher sTNFRI levels [mean pg/ml (95% CI)] were detected in patients receiving rhIL-11 compared to placebo [1749.7 (1626-1882.9) versus 1038.5 (953.3-1131.3)] respectively (P = 0.01) for all 898 observations and during febrile days [2327.6 (2142.6-2528.2) versus 1308.9 (1163-1473.2), P = 0.12] and during days without infection [1406.6 (1266.1-1563) versus 871.3 (774.9-979.6), P < 0.001]. A similar pattern in CRP concentrations was observed. Multivariate analysis indicated rhIL-11 was associated with elevated sTNFRI or CRP independent of infectious episodes and other factors. 7 patients (all receiving placebo) of 40 had elevated TNFalpha levels. IL-6 and IL-8 levels were not substantially affected by rhIL-11. Bacteremia, fungal infections, and fever of unknown origin (FUO) were reduced in rhIL-11-treated patients. Given the role of sTNFRI in dampening the deleterious effects of a hyperactive TNFalpha environment, rhIL-11-induced upregulation of sTNFRI shedding is a potentially important mechanism for modulating immune and inflammatory responses in humans.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Biomarkers; C-Reactive Protein; Female; Humans; Interleukin-11; Interleukin-6; Interleukin-8; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Receptors, Tumor Necrosis Factor, Type I; Recombinant Proteins; Tumor Necrosis Factor-alpha

Interleukin 8 (IL-8) is highly expressed in refractory acute lymphocytic leukemia (ALL) cells. This study aimed to investigate the contribution of IL-8 polymorphisms to the risk of childhood ALL.. The genotypes of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were determined in 266 childhood ALL cases and 266 controls using the PCR-RFLP method. Additionally, we assessed whether the interactions of these genotypes with age and sex contributed to childhood ALL risk.. The distributions of genotypic and allelic frequencies of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were not significantly different between childhood ALL cases and controls (all p>0.05). However, carriers of the variant AA genotype at IL-8 rs4073 had a significantly higher risk of childhood ALL among those aged ≤3.5 years and among girls (OR=2.39 and 3.32, 95%CI=1.21-4.73 and 1.51-7.30, p=0.0182 and 0.0042, respectively). In the stratification analysis, IL-8 rs4073 AT and AA genotypes were associated with higher childhood ALL risk classification and shorter survival time (OR=2.21 and 4.13, 95%CI=1.29-3.78 and 1.87-9.10, p=0.0054 and 0.0002, respectively). There was no positive association for rs2227306, rs2227543, or rs1126647 (all p>0.05).. The A allele of IL-8 rs4073 can serve as a diagnostic predictor for childhood ALL, but only in girls and patients younger than or equal to 3.5 years old. More importantly, it can serve as a prognostic marker for high-risk classification and shorter survival time. Further validation studies can help extend the use of this prognostic predictor in clinical practice.

Topics: Case-Control Studies; Female; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis

The present study was designed to assess whether raised Serine protease inhibitor Kazal type 1 (SPINK1) expressions modulates angiogenesis. Human umbilical vein endothelial cells (HUVECs) exposed to SPINK1 were noted to exhibit raised expressions of interleukin-8 (IL-8) as well as VCAM-1 and ICAM-1 cell adhesion molecules in a dose-dependent manner. In co-culture system of HUVECs and Acute lymphoblastic leukemia (ALL) cells, SPINK1 exposure also resulted in enhanced endothelial cell motility and ALL cells trans-endothelial migration. High concentrations of SPINK1 caused in vitro cellular reorganization into tubes in Matrigel-cultured HUVECs and induced in vivo vascularization and brain infiltration of NOD/SCID ALL model mice. The further transcriptomic analysis indicated that SPINK1 treatment altered several biological processes of endothelial cells and led to activation of the MAPK pathway. This study is the first to determine the neovascularization effects of raised SPINK1.

Topics: Animals; Cell Movement; Coculture Techniques; Disease Models, Animal; Endothelial Cells; Female; Gene Expression; Human Umbilical Vein Endothelial Cells; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; MAP Kinase Signaling System; Mice; Mice, Inbred NOD; Mice, SCID; Neovascularization, Pathologic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trypsin Inhibitor, Kazal Pancreatic; Vascular Cell Adhesion Molecule-1

To investigate the effect of interleukin -8 (IL-8) on immune function in acute lymphoblastic leukemia patients and its related mechanisms.. Forty-five ALL patients were selected from January 2014 to September 2017 in our hospital. Out of them, 32 relieved patients were included in group A, 13 patients did not relieved patients after treatment and were included in the group B. The serum IL-8 level was detected by ELISA.Th1 and Th2 cells were measured by flow cytometry. After Th cells were treated with different concentration of IL-8, the Western blot was used to detect the translation levels of p-STAT3 and JAK in cells.. The difference of white blood cell count and clinical risk level between the 2 groups was statistically significant (P<0.05). The serum IL-8 levels in group A and B were significantly higher than that in control group (P<0.05). The serum IL-8 level in group B was significantly higher than that in group A (P<0.05). After treatment, the level of Th1 cells in group B was 6.15%±1.22%, significantly lower than that in group A (P<0.05), and Th2 cell level in group B was 2.76%±0.24%, significantly higher than that in group A (P<0.05); Th1/Th2 in group B was 2.23%±0.09, significantly lower than that in group A (P<0.05). The protein level of p-STAT3 and JAK in the Th cells was lower than that in control group at different levels of IL-8 after treatment (P<0.05). After stimulating Th cells with 20 ng/ml IL-8, the levels of p-STAT3 and JAK protein in cells were lower than those after 10 ng/ml IL-8 treatment (P<0.05). IL-8 level had no significant effect on the protein expression of STAT3 in Th cells (P>0.05).. IL-8 can interfere the balance of Th1/Th2 through STAT3 signaling pathway, and has effect on the immune function of ALL patients.

Topics: Humans; Interferon-gamma; Interleukin-8; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Th1 Cells; Th2 Cells

Bacterial inflammation is a common complication in patients with leukemia, and sulfur dioxide (SO2) is a bioactive molecule in modulating Gram-negative bacilli infection. This study aimed to examine the changes in SO2, nuclear factor-κB (NF-κB), and interleukin-8 (IL-8) levels in pediatric acute lymphoblastic leukemia (ALL) with Gram-negative bacterial inflammation.. Fifty-five ALL children were enrolled in this study, including 30 males and 25 females, aged 3-13 years, and the median age was 7.8 years. All these children who accepted chemotherapy for ALL were divided into the control group (before chemotherapy), the infection group (after chemotherapy with infection), and the recovery group (the infection was controlled after 1 week). The serum level of SO2 was detected using high performance liquid chromatography with fluorescence assay, and NF-κB and IL-8 levels were measured by enzyme-linked immunosorbent assay (ELISA). Human THP-1 cells were cultured, induced, and differentiated into macrophages, which were divided into five groups and each group was cultured with different stimulators: lipopolysaccharide (LPS) group, LPS+L-aspartate-β-hydroxamate (HDX) group, LPS+SO2 group, SO2, and control groups. NF-κB level and IL-8 protein contents by ELISA were examined in each group.. In comparison with those of the control group, levels of serum SO2, NF-κB, and IL-8 of the infection group were significantly increased (P < 0.05), while those of the recovery group were significantly decreased (P < 0.05). A positive correlation was found between levels of serum SO2 and intracellular NF-κB/IL-8, and the correlation coefficients were 0.671 and 0.798 (P < 0.05), respectively. According to the results found in human THP-1 cells, levels of NF-κB and IL-8 in LPS group were significantly increased compared with those of the control group (P < 0.05); when compared with those in LPS group, levels of NF-κB in LPS+HDX group further increased significantly (P < 0.05); however, the NF-κB levels of LPS+SO2 group decreased significantly (P < 0.05).. SO2 may play an anti-inflammatory role during the process of inflammation by inhibiting the activation and transcription of NF-κB.

Topics: Adolescent; Bacterial Infections; Cell Line; Child; Child, Preschool; Female; Humans; Inflammation; Interleukin-8; Male; NF-kappa B; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sulfur Dioxide

Recently attention has been paid to the role of cytokines in clinical pathology, since they can mediate a wide variety of biological effects. For these reasons multiplex methods have been developed to simultaneously measure numerous cytokines in individual small volume specimens. The aim of the study was to assess the usefulness of flow cytometric analysis of cytokines in peripheral blood and bone marrow plasma with Cytometric Bead Array (CBA) kits.. The study involved 59 children. Tests were performed in peripheral blood and bone marrow plasma. Human Inflammatory Cytokine Kit (IL-8, -1β, -6, -10, TNF, -12p70) and Human Th₁/Th₂/Th₁₇ Cytokine Kit (IL-2, -4, -6, -10, TNF, INF-γ, -17A) (BD Bioscience) were used. Samples were analyzed on a Cytomics FC500 flow cytometer (Beckman Coulter).. In patients diagnosed for hemophagocytic lymphohistiocytosis (HLH) (n=10) and for acute lymphoblastic leukemia (ALL) (n=12) Human Inflammatory Cytokine Kit was used. In almost all samples individual cytokines were detected in a wide range of concentrations (0.47 - 653.74 pg/ml). In samples from patients suffering from allergy (n=12) and in healthy children (n=25) Human Th₁/Th₂/Th₁₇ Cytokine Kit was used. Detection of individual cytokines was much lower: concentration range 0.09-30.17 pg/ml.. Based on our analysis the CBA test is suitable for analysis of several cytokines in small volumes of samples. A simple flow cytometer can be used for this test. The CBA test is more suitable for samples with expected increased levels of cytokines. When the levels of cytokines are low, the sensitivity of the CBA test can be too low.

Topics: Biomarkers; Bone Marrow; Child; Child, Preschool; Cytokines; Female; Flow Cytometry; Humans; Hypersensitivity; Interleukin-2; Interleukin-8; Lymphohistiocytosis, Hemophagocytic; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reference Values; Retrospective Studies

The interactions of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells have a positive impact on leukemia cell survival. In the present study, we proposed to identify and investigate the role of molecules critically involved in leukemia--microenvironment crosstalk.. Gene expression profiling analyses of BM mesenchymal stem cells (BMMSC) were performed following stimulation by ALL cells. CCL2 and IL-8 plasma levels were evaluated from ALL patients and controls. Expression of the CCL2 and IL-8 receptors in ALL was determined by RT-PCR. The biological effects of CCL2, IL-8 or its neutralizing antibodies in primary precursor-B ALL and BMMSC cells were evaluated using in vitro assays.. Leukemia stimulation of BMMSC upregulated the expression of several inflammatory chemokines, including CCL2 and IL-8. The BM plasma levels of CCL2 and IL-8 in children at diagnosis were significantly higher than in healthy controls (P < 0.001). Functional studies revealed that CCL2 and IL-8 enhanced the capacity of BMMSC to support adhesion of ALL cells. CCL2 and IL-8 were also found to enhance BMMSC survival and to increase their proliferation. ALL cells were not directly affected by CCL2 or IL-8.. The leukemic BM microenvironment had increased levels of CCL2 and IL-8. These chemokines are known to have suppressive effects in normal hematopoiesis. Our data indicate that CCL2 and IL-8 have a positive impact on BMMSC survival, proliferation, and adhesiveness to ALL cells. Leukemia-associated CCL2 and IL-8 upregulation may represent one possible mechanism of microenvironment perversion in favor of ALL cells.

Topics: Bone Marrow Cells; Cell Adhesion; Cell Survival; Chemokine CCL2; Child; Child, Preschool; Female; Humans; Infant; Interleukin-8; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Signal Transduction

The aim of this study was to assess the value of procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-a), interleukin (IL)-1b, IL-8, and soluble TNF receptor II (sTNFRII) in early and rapid diagnosis of infection in neutropenic children with acute lymphoblastic leukemia (ALL) and to distinguish bacterial from viral infections.. The study included five groups (A, B, C, D, and E) of children with ALL undergoing intensive chemotherapy. Groups A and B consisted of neutropenic children with bacterial and viral infection, respectively. Groups C and D consisted of nonneutropenic children with bacterial and viral infection, respectively. Group E consisted of children without neutropenia and without fever.. In all groups, blood samples were collected upon admission and then for 7 days on a daily basis. Levels of CRP, PCT, TNF-a, IL-1b, IL-8, and sTNFRII were determined in all blood samples.. We found a highly significant difference in PCT levels between bacterial and nonbacterial episodes. Sensitivity and specificity of PCT were 94 and 96.5%, respectively.. Serial measurement of PCT levels on a daily basis seems to be helpful for early prediction of severe bacterial infections, monitoring febrile episodes regarding response to antibiotic therapy, and early detection of complications in the infectious process.

Topics: Adolescent; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Fever; Humans; Infant; Interleukin-1beta; Interleukin-8; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Precursors; Receptors, Tumor Necrosis Factor, Type II; ROC Curve; Tumor Necrosis Factor-alpha

In this study, we examined the gene expression of interleukin (IL)-8, CXCR3, and CXCR4 in leukemic cells from 100 children with relapsed B-cell progenitors (BCP) acute lymphoblastic leukemia (ALL), using quantitative real-time polymerase chain reaction (RT-PCR). IL-8, CXCR3, and CXCR4 were expressed in almost all bone marrow (BM) samples. The CXCR4 expression significantly correlated with known prognostic factors at relapse: time point and site of relapse. Patients who had a combined BM relapse (n=21) had lower IL-8 and CXCR4 expression than those who had an isolated BM relapse (n=79). The CXCR3 expression was higher in female patients (n=39) than in male patients (n=61). However, this did not reach prognostic relevance in relapsed ALL.

Topics: Bone Marrow; Child; DNA Primers; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Chemokine; Receptors, CXCR3; Receptors, CXCR4; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm

The immunosuppressive effect of cytotoxic drugs, basic therapeutic agents in the treatment of childhood acute leukemias, requires monitoring of the immune system following cessation of therapy. The cytokines are soluble proteins that play a key role in the immunoregulation of the lymphocyte function. The cytokines regulate growth, differentiation and function of various cells in normal conditions. The aim of our study was to estimate serum levels of IL-2, IL-6, IL-8, IL-10 and TNF-alpha in children with acute lymphoblastic leukemia (ALL) after cessation of chemotherapy. The study involved 150 children with ALL. This group consisted of: 30 children 1 month after treatment cessation; 30 children, 3 months later; 30 children 6 months later; 30 children, 9 months later and 30 children, 12 months later. The control group consisted of 30 healthy children. The levels of the cytokines under study were assayed using the immunoassay kits (R&D Systems, USA). During the study significant differences in TNF-alpha, IL-2 and IL-8 serum concentrations were observed among treated children and controls. However there were no differences in IL-6 and IL-10 concentrations.

Topics: Adolescent; Child; Child, Preschool; Humans; Interleukin-10; Interleukin-2; Interleukin-6; Interleukin-8; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reference Values; Retrospective Studies; Tumor Necrosis Factor-alpha

We report a rare case of a cute lymphoblasticleukemia (ALL) who developed dyspnea, neurological disturbance with illusions, pancytopenia, phagocytosis and coagulation disturbances following bacterial tonsillitis. The values of soluble interleukin-2 receptor (sIL-2R), IL-6 and IL-8 were also elevated. Her clinicolaboratory findings were similar to hemophagocytic lymphohistiocytosis (HLH), which is a cytokine disease induced by activated T cells and macrophages. Atypical HLH following bacterial tonsillitis should be kept in mind in leukemia patients.

Topics: Antigens, CD; Antineoplastic Agents; Blood Coagulation; Child; Dyspnea; Female; Histiocytosis, Non-Langerhans-Cell; Humans; Interleukin-6; Interleukin-8; Pancytopenia; Phagocytosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas aeruginosa; Pseudomonas Infections; Receptors, Interleukin-2; Streptococcal Infections; Tonsillitis

Chemokines play an important role in leukocyte mobilization, hematopoiesis, and angiogenesis. Tissue-specific expression of particular chemokines also influences tumor growth and metastasis. Here, the CC chemokine pulmonary and activation-regulated chemokine (PARC)/CCL18 was measured in pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Surprisingly, PARC immunoreactivity was consistently detected in plasma from healthy donors. After purification to homogeneity, the presence of intact PARC (1-69) and processed PARC (1-68) in normal human plasma was confirmed by sequence and mass spectrometry analysis. Furthermore, PARC serum levels were significantly increased in children with T-ALL and prepreB-ALL compared to control serum samples, whereas serum levels in AML and preB-ALL patients were not significantly different from controls. In contrast, the hemofiltrate CC chemokine-1 (HCC-1)/CCL14 was not found to be a biomarker in any of these patients' strata, whereas the cytokine interleukin-6 (IL-6) was significantly decreased in AML and prepreB-ALL. Stimulated leukocytic cell lines or lymphoblasts from patients produced IL-8/CXCL8 or macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3) but not PARC, not even after IL-4 or IL-10 treatment. However, PARC was produced by superantigen or IL-4 stimulated monocytes co-cultured with lymphocytes or lymphoblastic cells. Serum PARC levels thus constitute a novel leukemia marker, possibly reflecting tumor/host cell interactions in the circulation.

Topics: Biomarkers, Tumor; Cell Line, Tumor; Chemokines, CC; Child; Child, Preschool; Coculture Techniques; Female; Humans; Immunohistochemistry; Infant; Interleukin-6; Interleukin-8; Leukemia, Myeloid, Acute; Lymphocytes; Male; Monocytes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Isoforms

To evaluate the expression of interleukin 8 (IL-8) and its A, B type receptors (IL-8RA, IL-8RB) in acute leukemia (AL).. Plasma IL-8 concentrations in peripheral blood and IL-8R expressions on bone marrow mononuclear cell (MNC) membrane of 77 newly diagnosed AL patients were assayed by ELISA and FACS, respectively. IL-8 concentration in cerebral spinal fluid (CSF) of 15 AL patients in complete remission (CR) were kinetically measured.. Plasma IL-8 levels in newly diagnosed AL patients were increased. IL-8 levels were higher in AML than in ALL, in AML-M4, M5 were higher than in AML-M1-M3, and in B-ALL were higher than in T-ALL, respectively (P < 0.05). In ALL, CR rate in patients with IL-8 > 100 ng/L was lower than in those with IL-8 < or = 100 ng/L (P < 0.05). 36.36% of the patients were MNC IL-8R positive. Peripheral blood WBC and blasts amounts in IL-8R(+) group were significantly higher than IL-8R (-) group (P < 0.05). CSF IL-8 levels in CR patients were not different from newly diagnosed patients (P > 0.05) and were increased while central nervous system leukemia (CNSL) developed.. Detection of IL-8 and IL-8R might help to identify AL types and predict prognosis and the development of CNSL.

Topics: Adolescent; Adult; Aged; Central Nervous System; Female; Follow-Up Studies; Humans; Interleukin-8; Leukemia, Myeloid, Acute; Leukemic Infiltration; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Interleukin-8A; Receptors, Interleukin-8B