interleukin-8 and Lymphoma--Non-Hodgkin

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

Non-Hodgkin's lymphoma (NHL) is a form of tumor that originates in the lymphoid tissues. Bacterial infections are very common in NHL patients. Because most of the patients do not experience apparent symptoms during the initial stage of infection, it is difficult to detect the underlying condition before it progresses to a more critical level. The activation of the cytokines is a hallmark of inflammation. Due to the advantages of short detection time and high sensitivity of cytokines, many studies have focused on relationship between cytokines and infection. However, few studies have been conducted on NHL patients with infection. Therefore, we reviewed the cytokine profiles of 229 newly diagnosed NHL patients and 40 healthy adults to predict respiratory bacterial infection and bacteremia. Our findings revealed that IL-6(41.67 vs 9.50 pg/mL), IL-8(15.55 vs 6.61 pg/mL), IL-10(8.02 vs 4.52 pg/mL),TNF-β(3.82 vs 2.96 pg/mL), IFN- γ(4.76 vs 2.96 pg/mL), body temperature(37.6 vs 36.5°C), CRP(20.80 vs 4.37 mg/L), and PCT(0.10 vs 0.04 ng/mL) levels were considerably greater in NHL cases with respiratory bacterial infections relative to NHL cases without infection (P<0.05). Furthermore, IL-6(145.00 vs 41.67 pg/mL), IL-8(34.60 vs 15.55 pg/mL),temperature(38.4 vs 37.6°C), PCT(0.79 vs 0.10 ng/mL), and CRP(93.70 vs 20.80 mg/L) levels in respiratory infectious NHL patients with more severe bacteremia were considerably elevated than in patients with respiratory bacterial infections only (P<0.05). Remarkably, increased levels of IL-6 and IL-8 are effective in determining whether or not pulmonary bacterial infectious NHL patients have bacteremia. Temperature, PCT, and CRP all have lower sensitivity and specificity than IL-6. IL-6 ≥18.79pg/mL indicates the presence of pulmonary bacterial infection in newly diagnosed NHL patients, and IL-6 ≥102.6pg/mL may suggest pulmonary bacterial infection with bacteremia. In short, this study shows that cytokines can be advantageous in the diagnosis and differentiation of pulmonary bacterial infection and bacteremia in newly diagnosed NHL patients and may also guide for the use of clinical antibiotics.

Topics: Adult; Bacteremia; Bacterial Infections; Cytokines; Humans; Interleukin-6; Interleukin-8; Lymphoma, Non-Hodgkin; Respiratory Tract Infections

We assessed the mechanism of hematopoietic stem cell (HSC) mobilization using etoposide with granulocyte-colony stimulating factor (G-CSF), and determined how this mechanism differs from that induced by cyclophosphamide with G-CSF or G-CSF alone.. We compared the clinical features of 173 non-Hodgkin's lymphoma patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT). Additionally, we performed in vitro experiments to assess the changes in human bone marrow stromal cells (hBMSCs), which support the HSCs in the bone marrow (BM) niche, following cyclophosphamide or etoposide exposure. We also performed animal studies under standardized conditions to ensure the following: exclude confounding factors, mimic the conditions in clinical practice, and identify the changes in the BM niche caused by etoposide-induced chemo-mobilization or other mobilization methods.. Retrospective analysis of the clinical data revealed that the etoposide with G-CSF mobilization group showed the highest yield of CD34+ cells and the lowest change in white blood cell counts during mobilization. In in vitro experiments, etoposide triggered interleukin (IL)-8 secretion from the BMSCs and caused long-term BMSC toxicity. To investigate the manner in which the hBMSC-released IL-8 affects hHSCs in the BM niche, we cultured hHSCs with or without IL-8, and found that the number of total, CD34+, and CD34+/CD45- cells in IL-8-treated cells was significantly higher than the respective number in hHSCs cultured without IL-8 (p = 0.014, 0.020, and 0.039, respectively). Additionally, the relative expression of CXCR2 (an IL-8 receptor), and mTOR and c-MYC (components of IL-8-related signaling pathways) increased 1 h after IL-8 treatment. In animal studies, the etoposide with G-CSF mobilization group presented higher IL-8-related cytokine and MMP9 expression and lower SDF-1 expression in the BM, compared to the groups not treated with etoposide.. Collectively, the unique mechanism of etoposide with G-CSF-induced mobilization is associated with IL-8 secretion from the BMSCs, which is responsible for the enhanced proliferation and mobilization of HSCs in the bone marrow; this was not observed with mobilization using cyclophosphamide with G-CSF or G-CSF alone. However, the long-term toxicity of etoposide toward BMSCs emphasizes the need for the development of more efficient and safe chemo-mobilization strategies.

Topics: Adolescent; Adult; Aged; Animals; Apoptosis; Bone Marrow; Cell Line; Cell Proliferation; Cyclophosphamide; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Interleukin-8; Leukocyte Count; Lymphoma, Non-Hodgkin; Male; Mesenchymal Stem Cells; Mice; Middle Aged; Models, Animal; Peripheral Blood Stem Cell Transplantation; Primary Cell Culture; Retrospective Studies; Transplantation, Autologous; Young Adult

To investigate the ovarian reserve in female lymphoma patients and the potential relationships with the cytokine network.. Age-matched control study.. Women's university hospital.. Seventy-three lymphoma patients (57 with classic Hodgkin lymphoma [HL] and 16 with non-Hodgkin lymphoma [NHL]), approaching our center for ovarian tissue cryopreservation (study group) were compared with 25 age-matched healthy volunteers (control group).. Measurements of antimüllerian hormone (AMH), soluble interleukin-2 receptor (SIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) levels.. The AMH and cytokine levels of the lymphoma patients and the healthy volunteers were compared. Correlations between AMH with SIL-2R, IL-6, and IL-8 levels were performed.. The AMH showed significant lower concentrations in lymphoma patients than in the control group. Higher significant concentrations in lymphoma patients than in control group were found for SIL-2R and IL-6. No differences were observed comparing HL and NHL groups and within the stages of HL group for AMH and all the cytokines analyzed. Finally, significant inverse correlations were observed in lymphoma patients between AMH and SIL-2R, IL-6, and IL-8 levels, but not with TNF-α levels. Positive correlations between SIL-2R with IL-6, and IL-6 with IL-8 were also shown.. In patients with HL or NHL at baseline the cytokine network is particularly active and the ovarian reserve is reduced. A strong negative correlation between AMH and SIL-2R, IL-6, and IL-8 has been also evidenced.

Topics: Adolescent; Adult; Anti-Mullerian Hormone; Biomarkers, Tumor; Case-Control Studies; Cohort Studies; Cytokines; Female; Fertility Preservation; Hodgkin Disease; Humans; Infertility, Female; Interleukin-6; Interleukin-8; Lymphoma, Non-Hodgkin; Ovarian Reserve; Ovary; Receptors, Interleukin-2; Tumor Necrosis Factor-alpha; Up-Regulation; Young Adult

We aimed to investigate any association between hepatitis C virus (HCV) infection and non-Hodgkin’s\ lymphoma (NHL) in the view of cytokines that control inflammation/angiogenesis and their correlation with\ certain CD markers. NHL patients with or without HCV infection were studied. CD5, CD30, CD3, CD20 and\ CD45 were immunohistochemically evaluated. Plasma levels of vascular endothelial and platelet derived growth\ factors (VEGF, and PDGF), tumor necrosis factor (TNF-α), transforming growth factor (TGF-β), interleukin-6\ (IL-6), IL-8, IL-4, IL-12 and interferon gamma (IFN-γ) were detected by enzyme-linked immunosorbent assay\ (ELISA). HCV+ve NHL patients showed a significant reduction in VEGF, PDGF, IFN-γ, CD5 and CD45 and a\ significant increase in IL-12 and IL-8. In conclusion, there was a significant change in cytokine secretion and\ expression of CD markers in HCV+ve NHL patients. Based on our results, HCV infection in NHL patients\ requires more in-depth investigations to explore any role in lymphoma progression.

Topics: Adolescent; Adult; Aged; Antigens, CD; Biomarkers, Tumor; Female; Hepacivirus; Hepatitis C; Humans; Inflammation; Interferon-gamma; Interleukin-12; Interleukin-4; Interleukin-6; Interleukin-8; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neovascularization, Pathologic; Platelet-Derived Growth Factor; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Young Adult

Angiogenesis plays an important role in many types of cancer. Interleukin-8 (IL-8) is known to be a pro-inflammatory and pro-angiogenic cytokine, and IL-8 has been reported to be associated with tumor progression, prognosis and survival in several types of cancers. However, the role of IL-8 in non-Hodgkin's lymphoma (NHL) has not been fully determined. Here, we evaluated the usefulness of measuring serum and urine IL-8 levels in patients with NHL. We developed reference intervals for serum and urine IL-8 level in 131 control individuals. We measured serum IL-8 and urine IL-8 levels in patients with NHL, and we compared the concentrations with those of control individuals. The reference intervals for serum IL-8 and urine IL-8 corrected by creatinine (Cr) were 15.9-430.3 pg/mL and 0.0-28.4 pg/mg Cr, respectively. The concentrations of urine IL-8/Cr were significantly higher in patients than in controls (48.9+/-194.4 vs. 5.2+/-13.8 pg/mg Cr, P<0.001). However, there were no significant differences in serum IL-8 concentrations between NHL patients and controls (159.2+/-40.4 vs. 99.6+/-107.1 pg/mL; P=0.099). Receiver operating characteristic (ROC) analysis gave 0.83 and 0.43 ROC area values for urine IL-8/Cr and serum IL-8, respectively. There was no correlation between the serum and urine concentrations of IL-8 and clinical variables, the only exception being the international prognostic index (IPI), which showed a marginal correlation with urine IL-8/Cr levels (P=0.07). This study indicated that urine IL-8/Cr levels might be useful as a diagnostic marker of NHL.

Topics: Adult; Aged; Biomarkers, Tumor; Creatinine; Female; Humans; Interleukin-8; Lymphoma, Non-Hodgkin; Male; Middle Aged; Reference Values; Remission Induction

Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia (MC) and B-cell non-Hodgkin's lymphoma (B-NHL), possibly because viral antigens stimulate the host's inflammatory response via extracellular pattern recognition receptors (PRR). To clarify this issue, we studied whether recognition of hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV-associated MC or B-NHL.. Peripheral blood mononuclear cells of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the recombinant HCV proteins E2, core, and NS3 to study induction of cytokine production, stimulation of B-cell proliferation, and immunoglobulin secretion. In addition, serum levels of interleukin-6 (IL-6) were measured by ELISA.. HCV core was the only studied protein, which induced production of IL-6 and IL-8 in CD14(+) cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and IL-6 serum concentrations were increased in all groups of HCV-infected patients compared with healthy controls and were highest in MC (P < 0.05).. Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play a role in the pathogenesis of hepatitis C-associated MC and B-NHL.

Topics: Adult; Aged; Aged, 80 and over; Cell Proliferation; Cryoglobulinemia; Female; Hepacivirus; Hepatitis C; Humans; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Middle Aged; Recombinant Proteins; Toll-Like Receptor 2; Up-Regulation; Viral Core Proteins

A 43-year-old female with large T-cell non-Hodgkin's lymphoma and central nervous system (CNS) involvement underwent HLA-identical-sibling peripheral blood stem cell transplantation (SCT) during her third complete remission. She presented a possible refractory CNS relapse 5 months after the transplant. She was then treated with intrathecal (IT) donor lymphocyte infusions (DLI). No side effects were observed after three DLI injections. The patient died 13 months later from infectious complications with no evidence of progressive disease. To our knowledge, this is the first case report of IT DLI for possible refractory lymphomatous meningitis.

Topics: Adult; Disease Progression; Female; HLA Antigens; Humans; Injections, Spinal; Interleukin-6; Interleukin-8; Lymphocyte Transfusion; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Magnetic Resonance Imaging; Meningitis; Remission Induction; Stem Cell Transplantation

Adherence of hematopoietic progenitor cells (HPCs) to stroma is an important regulatory step in megakaryocytic differentiation. However, the mechanisms through which megakaryocytic progenitors are inhibited by stroma are poorly understood. We examined the role of sulfated glycoconjugates, such as proteoglycans (PGs), on human bone marrow stroma (hBMS). To this end, PG structure was altered by desulfation or enzymatic cleavage. PGs participated in adhesion of human HPC, as desulfation resulted in about 50% decline in adhesion to hBMS. Heparan sulfate proteoglycans (HSPGs) were found to be responsible by showing about 25% decline in adhesion after pre-incubation of HPC with heparin and about 15% decline in adhesion after enzymatic removal of HSPGs from hBMS. Furthermore, PGs were involved in binding cytokines. Both desulfation and enzymatic removal of stromal HSPGs increased release of megakaryocytopoiesis-inhibiting cytokines, that is, interleukin-8 (IL-8, 1.9-fold increase) and macrophage inflammatory protein-1alpha (MIP-1alpha, 1.4-fold increase). The megakaryocytic output of HPC grown in conditioned medium of desulfated stroma was decreased to 50% of the megakaryocytic output in CM of sulfated stroma. From these studies, it can be concluded that PGs in bone marrow, in particular HSPGs, are involved in binding HPC and megakaryocytopoiesis-inhibiting cytokines. Bone marrow stromal PGs thus reduce differentiation of HPC toward megakaryocytes.

Topics: Acute Disease; Antigens, CD34; Blood Proteins; Bone Marrow; Cell Adhesion; Cell Differentiation; Cells, Cultured; Chemokine CCL3; Chemokine CCL4; Culture Media, Conditioned; Eosinophil Major Basic Protein; Hematopoietic Stem Cells; Heparitin Sulfate; Humans; Interleukin-8; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Macrophage Inflammatory Proteins; Megakaryocytes; Proteoglycans; Stromal Cells

Treatment with rituximab, a chimaeric anti-CD20 monoclonal antibody, can be associated with moderate to severe first-dose side-effects, notably in patients with high numbers of circulating tumour cells. The aim of this study was to elucidate the mechanism of these side-effects. At multiple early time points during the first infusion of rituximab, complement activation products (C3b/c and C4b/c) and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and IL-8] were measured in five relapsed low-grade non-Hodgkin's lymphoma (NHL) patients. Infusion of rituximab induced rapid complement activation, preceding the release of TNF-alpha, IL-6 and IL-8. Although the study group was small, the level of complement activation appeared to be correlated both with the number of circulating B cells prior to the infusion (r = 0.85; P = 0.07) and with the severity of the side-effects. We conclude that complement plays a pivotal role in the pathogenesis of side-effects of rituximab treatment. As complement activation can not be prevented by corticosteroids, it might be relevant to study the possible role of complement inhibitors during the first administration of rituximab.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Complement Activation; Complement C3b; Complement C3c; Complement C4; Complement C4b; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Lymphocyte Count; Lymphoma, Non-Hodgkin; Male; Middle Aged; Peptide Fragments; Rituximab; Stimulation, Chemical; Tumor Necrosis Factor-alpha

To study the clinical significance of serum cytokine levels in patients with malignant lymphoma(ML).. Serum levels of five cytokines and receptor were measured in 49 patients with ML by RIA and ELISA.. Except TNF alpha, significantly higher pretreatment levels of interleukin-2(IL-2), soluble interleukin-2 receptor(sIL-2R), interleukin-6(IL-6) and interleukin-8(IL-8) were observed in most of ML patients at diagnosis or relapse as compared with controls(P < 0.05). Cytokine levels declined in responding patients after therapy and there were no differences between CR cases and controls, the cytokine levels remained elevated in non-responding patients. The levels of IL-2 and sIL-2R correlated with the clinical stage, which were significantly higher in patients in stage III, IV. The increase of sIL-2R correlated with the tumor burden. The level of IL-6 was higher in patients presenting B symptoms and had no correlation with the clinical stage. The elevated IL-8 level correlated with the clinical stage and presenting B symptoms of ML patients and had no correlation with other clinical-hematological parameters.. The changes of cytokines may be served as a means to observe the condition of ML patients and supervise their response to treatment.

Topics: Adolescent; Adult; Aged; Female; Hodgkin Disease; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Lymphoma, Non-Hodgkin; Male; Middle Aged; Receptors, Interleukin-2; Tumor Necrosis Factor-alpha

Hodgkin's disease (HD) shows rare neoplastic Hodgkin and Reed-Sternberg cells embedded in an abundant reactive infiltrate containing, among other cell types, neutrophilic granulocytes. Interleukin (IL)-8 is chemotactic for neutrophils. The expression of IL-8 was tested by in situ hybridization with 35S-labeled IL-8-specific RNA probes on 38 cases of HD. Reactive lesions, non-Hodgkin's lymphomas of B and T phenotype, and Langerhans cell histiocytosis served as controls. IL-8 expression was observed in Hodgkin and Reed-Sternberg cells in 3 of 33 cases of classical HD and in reactive cells in 20 of 33 HD cases as evidenced by combined isotopic in situ hybridization and immunohistology for the demonstration of cell-type-characteristic antigens or enzyme histochemistry for chloroacetate esterase. IL-8-positive cells were more numerous in cases of nodular sclerosing HD as compared with the mixed cellularity histotype (P = 0.01). The number of IL-8-positive cells and the density of neutrophils were positively correlated (P < 0. 01). In 5 cases of lymphocyte-predominant HD, IL-8 expression was not displayed. Non-Hodgkin's lymphoma cases contained IL-8 transcripts only in 1 of 23 cases in sparse reactive cells. In 4 of 7 cases of Langerhans cell histiocytosis, IL-8-specific signals were displayed in S100-negative cells. In conclusion, IL-8 expression in HD is largely confined to reactive cells and associated with infiltration by neutrophils. Elaboration of other cytokines by Hodgkin and Reed-Sternberg cells and reactive cells may explain the frequent expression of this cytokine in HD, particularly in the nodular sclerosing type.

Topics: Cell Count; Histiocytosis, Langerhans-Cell; Hodgkin Disease; Humans; Interleukin-8; Lymphoma, Non-Hodgkin; Mycobacterium Infections; Neutrophils; Palatine Tonsil