interleukin-8 and Hodgkin-Disease

Nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD) are characterized by their association with Epstein-Barr virus (EBV) and the presence of an intense lymphoid stroma, consisting of T lymphocytes and other reactive cells. In both entities, the tumour cells express viral proteins known to provide target epitopes for cytotoxic T-cells (CTLs), yet in vivo, the tumour cells appear to escape CTL recognition. A comparative in situ hybridization study of cytokine and chemokine gene expression in NPC and HD has been undertaken, focusing on cytokines which are known to be inducible by EBV in vitro. Hodgkin and Reed-Sternberg (HRS) cells expressed interleukin (IL)-6, IL-8, and IL-10, and the thymus and activation regulated chemokine (TARC) in 15/22, 0/22, 5/22, and 16/21 cases, respectively. In NPC, the epithelial tumour cells showed expression of IL-6 in 3/43 cases and of IL-8 in 2/40 cases. There was no detectable expression of IL-10 and TARC in these cases. These data confirm that HRS cells frequently express cytokine and chemokine genes and suggest that this may enable HRS cells to modulate the immune response in their microenvironment and to escape CTL detection. In contrast, NPC tumour cells show only rare expression of IL-6 and IL-8 and no detectable expression of IL-10 and TARC. Thus, the results suggest that the mechanisms employed by the EBV-positive tumour cells to escape immune recognition and destruction differ between HD and NPC.

Topics: Carcinoma; Carcinoma, Squamous Cell; Chemokine CCL17; Chemokines, CC; Cytokines; Epstein-Barr Virus Infections; Gene Expression; Hodgkin Disease; Humans; Immunohistochemistry; In Situ Hybridization; Interleukin-10; Interleukin-6; Interleukin-8; Nasopharyngeal Neoplasms; Reed-Sternberg Cells; RNA, Messenger

In a search for specific serum markers with prognostic impact, we evaluated the clinical significance of IL-4, IL-7, and IL-8 as well as TNF receptor levels and soluble p53 in the serum of patients with untreated Hodgkin's lymphoma (HD). No elevations were observed for IL-4, while IL-7 and IL-8 were elevated in 15/52 (29%) and 21/78 (27%) patients, respectively. Soluble TNF receptors were detected in 16/29 patients (55%), and were significantly elevated in 6 (21%). P53 was detected in 21/33 (64%) patients. While IL-7 levels, detectable sTNF receptors, and p53 were not correlated with other obvious parameters, elevated IL-8 levels were associated with the presence of B symptoms (p < 0.002) and occurred more often in the nodular sclerosis form than in other histological subtypes (p < 0.02). Further investigations that correlate these serum parameters with the situation at the cellular level of an involved tissue will help to elucidate the enigmatic biology of HD.

Topics: Hodgkin Disease; Humans; Interleukin-7; Interleukin-8; Prognosis; Prospective Studies; Receptors, Tumor Necrosis Factor; Solubility; Tumor Suppressor Protein p53

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

Classical Hodgkin's lymphoma (cHL)-affected lymphoid tissue contains only a few malignant Hodgkin and Reed-Sternberg (HRS) cells, which are disseminated within a massive infiltrate of reactive cells. In particular, the innate immune infiltrate is deemed to support tumour growth by direct cell-cell interaction. Since they are rarely found in close proximity to the malignant cells in situ, we investigated whether cHL-derived extracellular vesicles might substitute for a direct cell-cell contact. We studied the crosstalk of the transmembrane proteins CD30 and CD30 ligand (CD30L) because they are selectively expressed on HRS and innate immune cells, respectively. Here, we showed that HRS cells released both the ectodomain as a soluble molecule (sCD30) and the entire receptor on the surface of extracellular vesicles. The vesicle diameter was 40-800 nm, as determined by cryo- and immune electron microscopy. In addition to CD30, typical extracellular vesicle markers were detected by mass spectrometry and flow cytometry, including tetraspanins, flotillins, heat shock proteins and adhesion molecules. In contrast to sCD30, vesicles caused a CD30-dependent release of interleukin-8 in CD30L(+) eosinophil-like EoL-1 cells and primary granulocytes from healthy donors, underscoring the functionality of CD30 on vesicles. In extracellular matrix (ECM)-embedded culture of HRS cells, a network of actin and tubulin-based protrusions guided CD30(+) vesicles into the micro-environment. This network targeted CD30(+) vesicles towards distant immune cells and caused a robust polarization of CD30L. Confocal laser scanning microscopy of 30 µm sections showed a CD30 vesicle-containing network also in cHL-affected lymphoid tissue of both mixed-cellularity and nodular sclerosing subtypes. This network might facilitate the communication between distant cell types in cHL tissue and allow a functional CD30-CD30L interaction in trans. The tubulin backbone of the network may provide a target for the therapy of cHL with antitubulin-based CD30 antibody constructs.

Topics: Biomarkers, Tumor; CD30 Ligand; Cell Communication; Cell Line, Tumor; Cell Surface Extensions; Cryoelectron Microscopy; Eosinophils; Flow Cytometry; Granulocytes; Hodgkin Disease; Humans; Interleukin-8; Ki-1 Antigen; Mass Spectrometry; Microscopy, Confocal; Microscopy, Electron, Transmission; Microscopy, Immunoelectron; Organelle Size; Reed-Sternberg Cells; Secretory Vesicles; Signal Transduction; Tumor Microenvironment

Eosinophils are seen together with neutrophils at sites of inflammation. However, their roles are not clear. In addition, eosinophils infiltrate tumor tissue in some neoplastic diseases. In this study, we show that large amounts of the neutrophil-activating CXC chemokine growth-related oncogene (GRO)-alpha can be produced by human eosinophils. Eosinophils showed presence of preformed GRO-alpha in the crystalloid-containing specific granules (190 pg/2 x 10(6) cells). During incubation, a strong increase in GRO-alpha gene expression was seen. At a low cell density, addition of TNF-alpha or IL-1 beta increased the production of GRO-alpha in eosinophils, which was not the case at a higher cell density. Eosinophils can produce TNF-alpha themselves, and neutralizing Abs against TNF-alpha significantly inhibited GRO-alpha production. This suggests that autocrine and paracrine effects from TNF-alpha can be important when up-regulating GRO-alpha gene expression. In contrast, IFN-gamma, a prototypic Th1-cytokine, down-regulated expression of GRO-alpha. This may be important during resolution of inflammation but also suggests different roles for eosinophils depending on the inflammatory context. Tumor-infiltrating eosinophils in Hodgkin's disease of the nodular sclerosing type are associated with a poor prognosis. Eosinophils from such tumor tissue showed an abundant expression of GRO-alpha. The GRO-alpha receptor CXCR2 was also detected in tumor tissue, proposing interactions between eosinophils and the tumor. Our findings suggest that eosinophils can promote inflammation through recruitment of CXCR2-bearing cells. In addition, this feature of the eosinophils indicates a role for these cells in the biology of certain tumors.

Topics: Autocrine Communication; Cell Communication; Chemokine CXCL1; Chemokines; Chemokines, CXC; Chemotactic Factors; Down-Regulation; Eosinophils; Hodgkin Disease; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Interferon-gamma; Interleukin-5; Interleukin-8; Microscopy, Immunoelectron; Neoplasm Proteins; Paracrine Communication; Rhinitis, Allergic, Seasonal; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation

Monocyte chemotactic protein 1 (MCP-1) and interleukin 8 (IL-8) are small, inducible proteins with chemotactic activity for specific subsets of leucocytes. The possibility that MCP-1 and IL-8 are produced in tissues involved by Hodgkin's disease, thus contributing to the inflammatory-type background of the lesion, was investigated.. The presence of RNA transcripts for MCP-1 and IL-8 was investigated in biopsy samples of 24 cases of Hodgkin's disease, 17 non-Hodgkin's malignant lymphomas, 30 solid tumours, and 30 histologically normal tissues by means of reverse transcription-polymerase chain reaction (RT-PCR)/Southern blot analysis.. MCP-1 expression was detected in 23 of 24 cases of Hodgkin's disease, in seven of 17 cases of B cell non-Hodgkin's lymphoma, and in seven of 14 cases of reactive lymphoid hyperplasia. IL-8 was present in six of 14 cases of Hodgkin's disease, and was seen only rarely in B cell non-Hodgkin's lymphoma and in reactive lymphoid tissues. MCP-1 and IL-8 RNA transcripts were detected in 13 of 25 carcinomas originating from the lung, breast, thyroid, and ovary.. These findings are consistent with the possibility that MCP-1 and IL-8 are two additional cytokines involved in the pathogenesis of Hodgkin's disease.

Topics: Blotting, Southern; Chemokine CCL2; Female; Hodgkin Disease; Humans; Interleukin-8; Lymphoma, B-Cell; Neoplasm Proteins; Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

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

It has been suggested that cytokines are involved in the pathogenesis of Hodgkin's disease. Enhanced expression of various cytokines has been demonstrated in cell lines and biopsy specimens from patients with Hodgkin's disease (HD).. In this investigation 14 cytokines were analysed by ELISA in sera of a large panel of patients with HD and compared with clinical and serological parameters.. Increased levels of soluble IL-2 receptors (sIL-2R), IL-6, IL-7, IL-8 and G-CSF, were found in many patients with HD as opposed to healthy individuals. In contrast, IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, TNF alpha, TNF beta and GM-CSF were rarely detectable. Serum concentrations of sIL-2R, IL-6 and IL-7 were significantly correlated with advanced stage of HD and, together with G-CSF levels, with the presence of B-symptoms. In addition, elevated cytokines correlated with several laboratory parameters. In the majority of patients the serum levels of cytokines decreased after therapy. However, elevated cytokine levels persisted in some patients in complete remission. Patients with normal IL-6 levels had better event-free survivals than patients with elevated IL-6 levels but this difference has not reached significance.. Our results indicate that enhanced levels of sIL-2R, IL-6, IL-7, IL-8 and G-CSF, are correlated with disease activity and clinical symptoms in HD.

Topics: Adolescent; Adult; Aged; Cytokines; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Female; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Interleukin-5; Interleukin-7; Interleukin-8; Male; Middle Aged; Prognosis; Receptors, Interleukin-2; Solubility