Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A bispecific antibody directed to T and B cells (CD3 x CD19 bsAb) was daily infused intravenously in escalating doses from 10 micrograms up to 5 mg in three patients with chemotherapy-resistant non-Hodgkin lymphoma; in this way we aimed to activate T cells to kill the malignant B cells. Only limited toxicity was observed, consisting of moderate fever preceded by chills or shivers and mild thrombocytopenia. No human anti-(mouse Ig) antibodies were found. Pharmacokinetics showed a t1/2 of 10.5 h with peak levels of 200-300 ng/ml after infusion of 2.5 mg bsAb. bsAb in serum was functionally active in vitro. After bsAb infusion a rise in serum tumour necrosis factor alpha was observed, accompanied by an increase in soluble CD8 and to some extent in soluble interleukin-2 receptor (IL-2R), but not in interferon gamma. IL-4 or soluble CD4. No evidence was found for monocyte activation (no increases in IL-6, IL-8 or IL-1 beta in serum). No gross changes in histology or number of IL-2R+, CD4+ or CD8+ cells were found in the lymph nodes after therapy, but one patient showed activated CD8+ T cells within the tumour nodules. In conclusion, after intravenously administered CD3 x CD19 bsAb only moderate toxicity was found, probably due to CD8+ T cell activation and cytokine release, without CD4+ T cell activation.
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PMID:CD8 T cell activation after intravenous administration of CD3 x CD19 bispecific antibody in patients with non-Hodgkin lymphoma. 754 21

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55

Highly enriched CD4+ and CD8+ human T cells were obtained from peripheral blood using a relatively simple and inexpensive method consisting of four steps: separation of mononuclear cells on Lymphoprep, removal of adherent monocytes by incubation in plastic petri dishes, removal of B cells, NK cells and further depletion of nonadherent monocytes by panning with anti-CD19, -CD16, -CD14, -CD11b and -CD33 mAb, and separation of CD4+ and CD8+ T lymphocytes by magnetic cell sorting (MACS). Cell culture for up to 48 h showed preservation of function by both positively and negatively selected cells as determined by production of IL-8. Although the cell separation procedure had no effect on interleukin-2 receptor (IL-2R, CD25) expression, it induced production of IL-4 by both T cell subsets selected positively, implying cell activation by ligation of CD4 and CD8 molecules. Irrespective of the mode of separation, CD8+ T cells produced more IL-4, a cytokine which is associated with a Th2-type cytokine profile of CD4+ T cells. We conclude that our method for separating T cells into their CD4+ and CD8+ subsets results in high cell purities with preservation of function, as determined by cytokine generation. If enriched cells are to be used for functional studies we recommend isolation by negative selection which has less effect on cell function. The relevance of the finding that CD8+ T cells can be an important source of IL-4 remains to be elucidated.
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PMID:Production of IL-8 and IL-4 by positively and negatively selected CD4+ and CD8+ human T cells following a four-step cell separation method including magnetic cell sorting (MACS). 857 72

In extensive preclinical testing, a CD3 x CD19 bispecific antibody (BsAb) induced killing of malignant B cells by resting T cells even in an autologous situation. In a 14 day clonogenic assay using a CD19+ pre-B cell line (REH), BsAb required repeated administration together with IL-2 to achieve a 5 log kill by resting peripheral blood T cells. Intravenously administered BsAb in an intrapatient dose escalation study of 3 patients with B cell non-Hodgkin's lymphoma showed limited toxicity (WHO grade II fever and chills) due to tumor necrosis factor-alpha (TNF-alpha) release by T cells. Pharmacokinetics with 2.5 mg BsAb showed peak levels of 200-300 micrograms/ml and a t1/2 of 10.5 h. The next patient, with chronic lymphocytic leukemia (CLL), received 0.6 mg BsAb/m2 as an i.v. infusion preceded by 1 MU IL-2/m2 s.c. Improved T cell activation was noted, as indicated by an increase in IFN-gamma, IL-6, IL-8, and IL-10, in addition to high TNF-alpha increases. TNF-alpha increases were highest on the first day. Toxicity remained restricted to grade II fever and chills, observed every day after the infusion of BsAb. No clear clinical effects were seen in this chemotherapy-resistant CLL patient with a high tumor burden. If subsequent patients also show limited toxicity, treatment of patients with a lower tumor load seems to be warranted to evaluate the efficacy of CD3 x CD19 BsAb therapy.
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PMID:Clinical experience with CD3 x CD19 bispecific antibodies in patients with B cell malignancies. 858 81

Our study investigated the presence of IL-8 in pleural exudates from tuberculosis patients (TBP) (n = 13), and evaluated whether it was related with the profile of major immunocompetent cells present in their pleural and peripheral compartments. To allow comparisons, an additional group of patients with parapneumonic pleural effusions (PNE) (n = 7) was included. Blood peripheral immunophenotypic studies were also carried out in 12 age-matched healthy controls (Co), and 39 tuberculosis patients classified, according to the extent of pulmonary involvement, into mild (n = 9), and advanced (n = 30) cases. Patients were recruited before starting therapy, had HIV negative serology, and showed no age differences among groups (mean +/- SD., 40.7 +/- 14.7 years). IL-8 concentrations were measured by an ELISA method while immunophenotypic analysis was performed by using FITC-conjugated monoclonal antibodies reacting against the following cell surface molecules: CD3, CD4, CD8, CD25 (IL-2R+ cells), CD19, and CD68. IL-8 was detected in all pleural exudates though levels in the TB patients, 384 +/- 110 pg/ml, appeared significantly higher than the PNE group, 185 +/- 110 pg/mg, (P < 0.015, mean +/- S.D.). In turn, the former group presented values of pleural CD3+, CD4+, and CD25, which were found increased in comparison with PNE patients (P < 0.01). Unlike the pleural compartment, patients with TBP showed a marked and significant decrease in their circulating levels of cells bearing the CD3, CD4, CD19, CD25, and CD68 phenotypes not only when comparing with Co but also with PNE and mild patients. Differences between the levels of pleural and peripheral T-cells from TBP patients may be the reflection of an important influx of T-lymphocytes from the circulatory system to the pleural cavity, probably linked to the presence of chemotactic factors within the pleural fluid like IL-8.
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PMID:Levels of interleukin-8 in tuberculous pleurisy and the profile of immunocompetent cells in pleural and peripheral compartments. 909 79

Rheumatoid arthritis arises from a reaction of the immune system to normal body components, sometimes triggered by bacterial or viral infection. The synovia of affected joints are infiltrated by CD4+, CD19-, and plasma cells. The synovial fluid shows a sterile inflammation, with high neutrophil counts and increased concentrations of proinflammatory cytokines (particularly IL-1, IL-8, TNF-alpha and JFN-gamma). The plasma shows increased CD4+ counts and a pro-inflammatory shift in T cell populations with high titers of rheumatoid factors. Traditional treatment has included rest of the affected part, which can cause a reduction of physical condition. However, exercise induces changes in circulating immune function (including a decrease of CD4+ count) that would appear helpful in regulating inflammation. Further, there is evidence that patients can tolerate a program of regular moderate aerobic exercise. Moreover, empirical data suggest that such a prescription substantially enhances physical performance, without exacerbating either clinical or immunological markers of the disease process.
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PMID:Autoimmune disorders, physical activity, and training, with particular reference to rheumatoid arthritis. 913 53

The immune system changes during the lifespan of man. Many described changes in the immune system of the elderly were dependent on illness or chronic diseases. To exclude these pathological changes in the immune system and to exclusively describe age-dependent changes, Ligthart et al. defined immunogerontological criteria to study the immune system in the elderly, the SENIEUR-Protocol. Most changes in the immune system of elderly are within the normal ranges of the appropriate parameter. However, there are many significant differences between the status of the immune system in healthy young and elderly individuals, within these normal ranges. The comparison between SENIEUR-elderly and healthy young and the additional comparison of these two groups with centenarians allows the discussion of potential pathological effects of these changes. In this article we summarize the described changes of the immune system in SENIEUR-elderly and centenarians. The serum levels of the immunoglobulins G, M and A increased with age, as well as the number of benign monoclonal gammopathies and the number of autoantibodies. The titers of zinc are significantly decreased in the serum of the elderly. The production of the acute phase protein C-reactive protein is not age-dependent, whereas the serum levels of alpha 2-macroglobulin are significantly increased in the elderly. The number of lymphocytes decreased and the number of neutrophils increased with aging. Monocytes, basophils, and eosinophils are without changes during life. There are many descriptions about changes of the leukocyte sub-population in aging, which are not always comparable. However, the number of T cells (CD3) decreases. Within the T cells the CD8 cells decreased more than the CD4 cells, resulting in an increased CD4/CD8 ratio. Memory T cells (CD45RO) increase during life, whereas naive T cells (CD45RA) decrease. Interestingly, centenarians have more naive T cells SENIEUR-elderly. The number of B cells (CD19) decreased also, whereas the number of natural killer (NK) cells (CD16, CD56, CD57) increases with aging. The capacity of leukocytes from the elderly to produce cytokines is also significantly different from those of the young. The release of the TH1-cytokines interleukin (IL)-2 and interferon (IFN)-gamma is decreased, whereas the production of the TH2-cytokines IL-4 and IL-10 is increased in the elderly. The production of proinflammatory cytokines such as IL-1, IL-6, IL-8, and tumor necrosis factor-alpha is increased in the elderly. In contrast, the capacity to produce the antiviral cytokine IFN-alpha is reduced in elderly individuals. In conclusion, the immune system shows many age-dependent changes, but we know little about the reason and the potential pathological effects of these changes.
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PMID:[Characteristics of immunologic test values in the elderly]. 933 53

Bispecific antibodies (BsAb) consist of two different heavy and light chains and may bind to two different antigens present on different cell types. With their dual specificity BsAb may recognize effector cells (e.g. T cells) on one hand and tumour cells (e.g. malignant B cells) on the other hand. The authors analysed whether T cell activation and subsequent killing of malignant B cells mediated by the bispecific antibody CD3 x CD19 was reflected by the release of cytokines. In addition, the authors investigated whether the in vitro cytokine release was similar to that observed in vivo in the patients treated with BsAb. The in vitro release of cytokines into the supernatant of cell cultures of peripheral blood mononuclear cells (PBMC) and malignant B cells was measured after incubation with either the bispecific antibody CD3 x CD19 or the monospecific anti-CD3 (aCD3) antibody in the presence or absence of interleukin (IL)-2. Release of tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, IL-8, IL-10, soluble (s) CD4, sCD8 and sCD25 by PBMC was equal under both conditions and could be used as an indicator for T cell activation. However, the cytokine pattern and level did not correlate with the cytotoxic capacity, which was 4 logs higher with BsAb + IL-2 compared to aCD3 + IL-2. The in vitro pattern of cytokine release was similar to that observed in vivo in the serum of patients treated with BsAb and IL-2, indicating the possibility of predicting cytokine release in future patients with other therapeutic regimens.
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PMID:Release of cytokines and soluble cell surface molecules by PBMC after activation with the bispecific antibody CD3 x CD19. 939 27

To clarify the cytokine profile of tonsils, cytokine mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA of interleukin-1 beta (IL 1 beta), IL-2, IL-4, IL-6, IL-8, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were expressed on the whole tonsillar tissue of all 5 subjects with recurrent tonsillitis, obstructive sleep apnea syndrome caused by tonsillar hypertrophy or tonsillar focal infection. These cytokine mRNAs were detected in tonsillar mononuclear cells freshly isolated from all or 14 of 15 subjects. The CD4, CD8 and CD19-positive cells were purified using immunomagnetic beads. The CD4-positive cells expressed mRNA of IL-1 beta, IL-2, IL-4, IL-8, IFN-gamma and TNF-alpha. The CD8-positive cells expressed mRNA of IFN-gamma and TNF-alpha. The CD19-positive cells expressed mRNA of IL-1 beta, IL-6, IL-8 and TNF-alpha. Quantitative measurement of PCR products in tonsillar mononuclear cells revealed that the IL-8 mRNA was expressed at a higher level than any other cytokine. A comparison among tonsillar diseases mentioned above revealed that the IL-1 beta and TNF-alpha mRNA were expressed at significantly higher levels in tonsillar mononuclear cells from patients with recurrent tonsillitis than in patients with obstructive sleep apnea syndrome caused by tonsillar hypertrophy. These data indicate that tonsils are active immunologic organs containing a wide variety of cytokines.
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PMID:[A study of cytokine in palatine tonsil--cytokine mRNA expression determined by RT-PCR]. 1019 27

Using two-color flow cytometry, we measured intracellular expression of interleukin-1 alpha (IL-1 alpha), IL-2, IL-4, IL-6, IL-8, interferon gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in tonsillar mononuclear cells freshly isolated and stimulated by phorbol myristate acetate (PMA) and ionomycin. In freshly isolated tonsillar mononuclear cells, IL-1 alpha was produced in 0.39% of CD3 cells, 0.48% of CD4 cells, 0.66% of CD19 and 11.2% of CD14 cells; TNF-alpha was found in 5.4% of CD14 cells. After 8-hour culture without any mitogens, IL-4, IL-8, TNF-alpha and IL-1 alpha were detected in 2.1%, 0.8%, 0.55%, and 0.42% of tonsillar mononuclear cells, respectively. Flow cytometric detection of intracellular cytokines in tonsillar mononuclear cells stimulated with PMA and ionomycin revealed that CD3 cells produced IL-1 alpha, IL-2, IL-4, IL-8, IFN-gamma and TNF-alpha, and CD19 cells produced IL-1 alpha, IL-6, IL-8 and TFN-alpha. In CD3 cells, the number of cells producing IL-2 and TNF-alpha were significantly higher than those expressing other cytokines; and the number of cells producing IFN-gamma and IL-8 were significantly higher than those expressing IL-4 and IL-1 alpha. In CD19 cells, the number of cells producing IL-6 and TNF-alpha were significantly higher than those of IL-8 and IL-1 alpha; and the number of cells producing IL-8 was significantly higher than that of IL-1 alpha. There was no difference in the number of CD3 and CD19 cells producing any cytokine between the adult recurrent tonsillitis group and adult obstructive sleep apnea syndrome group. However, the number of CD3 cells producing IL-2 or TNF-alpha and CD19 cells producing IL-1 alpha, IL-6 or TNF-alpha were significantly lower in children than that of adults (p < 0.05). These findings indicate that the cytokine production in tonsillar mononuclear cells is heterogenous according to the subset and activation and that flow cytometric analysis of intracellular cytokines is a useful means to investigate the pathophysiological role of cytokines in the tonsils.
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PMID:[A study of cytokine in palatine tonsil--flow cytometric analysis of cytokine production in tonsillar mononuclear cells]. 1019 28


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