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)

In this paper we describe the case of a 16-year-old boy with childhood onset cyclic neutropenia (CN) with a 21 d cycle who was successfully treated with recombinant granulocyte-colony stimulating factor (G-CSF). Cyclic therapy with G-CSF (5 micrograms/kg/d s.c. for 1 week every 21 d) maintained peripheral neutrophil count above the normal range, reduced the incidence of severe infections and significantly improved the patient's performance status throughout an 18-month follow-up. Phenotypic analysis of circulating lymphocytes demonstrated that G-CSF treatment does not modify the phenotypic profile of circulating B, T and NK cell populations. Circulating neutrophils released normal amounts of cytokines (including IL-1 beta, IL-8, TNF alpha) and superoxide anion during G-CSF therapy.
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PMID:Childhood onset cyclic neutropenia: G-CSF therapy restores neutrophil count but does not influence superoxide anion and cytokine release by neutrophils. 753 83

The production of nitric oxide (NO) is increased in experimental nephritis, with NO thought to be an important mediator of cell damage. The cytokines interleukin 1 beta (IL-1 beta), IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1) and transforming growth factor-beta (TGF-beta) are released from mesangial cells in vitro or are expressed in various forms of glomerulonephritis. We investigated the effects of these cytokines on NO synthesis in cultured rat mesangial cells. Incubation of mesangial cells with IL-1 beta (10 ng/ml) for 24 h increased the accumulation of NO and guanosine 3',5'-cyclic monophosphate (cGMP). IL-6, IL-8, MCP-1 and TGF-beta showed no significant effect on the production of NO or cGMP. Transcripts of the inducible NO synthase (iNOS) gene were not detected in unstimulated mesangial cells. However, exposure of cells to IL-1 beta (10 ng/ml) for 24 h resulted in the appearance of iNos mRNA. IL-1 beta-induced NO synthesis was significantly inhibited by NG-monomethyl-L-arginine, cycloheximide, actinomycin D, dexamethasone, and TGF-beta. These results indicate that, of the various cytokines studied, only IL-1 beta stimulates iNOS mRNA accumulation and NO synthesis in mesangial cells. NO may function in an autocrine manner to modulate the glomerular response to inflammation.
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PMID:Nitric oxide synthesis in rat mesangial cells induced by cytokines. 753 90

Differentiation induction therapy is used in myelodysplastic syndromes (MDS) to improve maturation defects and to restore impaired function of malignant cells. To this end, 18 patients with MDS received either a combination therapy consisting in study 1 of all-trans retinoic acid (ATRA) and granulocyte-colony stimulating factor (G-CSF), or in study 2 of a combination with ATRA, G-CSF, erythropoietin (Epo) and tocopherol. The ANC increased in 19/20 patients in both studies, whereas an increase in haemoglobin concentration, platelet counts or reduction of transfusion requirement was seen in only 8/20 patients, correlating strongly with good BFU-E growth (P < 0.001). To assess the role of accessory cells in the modulation of the haemopoietic response to treatment, we analysed the capacity of peripheral blood monocytes to secrete cytokines (IL-1 beta, IL-6, IL-8, TNF alpha). Secretion of all cytokines was significantly reduced before therapy when compared with healthy controls, but increased during therapy, reaching normal levels for IL-8. These data indicate that a combination therapy with ATRA and cytokines improves impaired cytokine secretion from monocytes and induces a multilineage clinical response in a subgroup of MDS patients characterized by an almost intact erythroid compartment. In contrast, induction of TNF alpha might be responsible for treatment failure.
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PMID:Changes in erythroid progenitor cell and accessory cell compartments in patients with myelodysplastic syndromes during treatment with all-trans retinoic acid and haemopoietic growth factors. 855 92

Allergic diseases such as allergen-induced rhinitis represent an inflammatory reaction that is characterized by the chemotaxis and activation of various cell populations. A high degree of cell-to-cell communication is needed to orchestrate this inflammatory immune response. A variety of cytokines and adhesion receptors seem to play an important role in the allergic late phase reaction. Here we demonstrate that proinflammatory cytokines such as interleukin(IL)-1, IL-8 and TNF-alpha (tumor necrosis factor-alpha) can be detected in nasal secretions and mucosa by enzyme-linked immunosorbent assay and immunohistochemistry. The increased expression of adhesion receptors in mucosa specimens of patients with seasonal allergic rhinitis points to their role in regulating the cellular migration and probably represents a key event in allergic inflammation. We established an in vitro model using freshly taken nasal mucosa to study the induction of adhesion receptors by proinflammatory cytokines. E-selectin, an endothelial receptor, was strongly upregulated by IL-1 beta, TNF-alpha and allergen. The induction due to allergen exposure of the mucosa was markedly inhibited by soluble cytokine receptors (sIL-1R, TNF-BP) or by a receptor antagonist (IL-1ra) and prednisolone, These findings indicate that proinflammatory cytokines may be key factors for the upregulation of adhesion processes in human nasal mucosa and the activation of various cell populations involved in the allergic inflammation. They therefore represent a main target for new therapeutic strategies.
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PMID:Proinflammatory cytokines in allergic rhinitis. 753 66

Bronchopulmonary disease in patients with cystic fibrosis (CF) is a paradigm of neutrophil-dominated airway inflammation. We hypothesized that proinflammatory cytokines contribute to a localized neutrophil-dominated inflammatory state as present in CF airways. In a cross-sectional study, we analyzed 63 sputum samples from 33 CF patients for concentrations of the cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), and granulocyte-colony stimulating factor (G-CSF) by means of enzyme-linked immunosorbent assay. Furthermore, the activity of neutrophil elastase (NE) in the sputum samples was determined using a specific chromogenic substrate. Compared to sputum samples from 10 healthy controls, there were significantly increased concentrations of IL-1 beta, IL-8 and TNF-alpha in the CF sputum samples. The concentration of IL-8 correlated significantly with NE activity in the CF sputum samples. In CF patients with airways chronically colonized with Pseudomonas aeruginosa, IL-8 concentrations in sputum were significantly enhanced. In glucocorticoid-treated patients, IL-1 alpha and G-CSF sputum concentrations were significantly lower when compared to levels in the other patients. These results show that there are high concentrations of proinflammatory cytokines in CF airways which may contribute to the localized neutrophil-dominated inflammatory state found clinically.
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PMID:Cytokines in neutrophil-dominated airway inflammation in patients with cystic fibrosis. 753 67

In the present study, we investigated the role of resident cells in the neutrophil migration induced by ovalbumin (OVA) in immunized rats. OVA administration induced dose-dependent neutrophil migration, which was inhibited by pretreating the animals with dexamethasone, but not with indomethacin or BW 70C. Lymphocytes, but not macrophages or mast cells, obtained from sensitized animals and stimulated in vitro with OVA released a factor that induced neutrophil migration in vivo and in vitro. Both the release of this factor in vitro and the neutrophil migration induced in vivo were inhibited by dexamethasone, thus explaining the inhibitory effect of glucocorticoids on the neutrophil migration induced by OVA in immunized animals. Neither indomethacin nor BW 70C had any such effect. The fact that actinomycin D also inhibited the release of the factor from OVA-stimulated lymphocytes suggests that this substance is of a proteinaceous nature. The importance of lymphocytes for neutrophil recruitment in OVA-immunized rats was supported by the fact that homologous lymphocyte transfer into air pouches rendered these cavities responsive to OVA. Lymphocytes obtained from naive rats and stimulated with the lectins concanavalin A (Con A) or phytohaemagglutinin (PHA) were also able to release a factor that induced neutrophil migration in vivo. In vitro incubation of the supernatant from OVA-stimulated lymphocytes with antisera to interleukin-1 beta (IL-1 beta), IL-8 and tumour necrosis factor-alpha (TNF-alpha) did not inhibit the neutrophil chemotactic activity. These data suggest that IL-1 beta, IL-8 and TNF-alpha are not involved in the neutrophil chemotactic activity of the supernatant. Overall, these results indicate the importance of lymphocyte participation in neutrophil recruitment during inflammatory immune reaction, through the release of a neutrophil chemotactic factor different from IL-1 beta, IL-8 and TNF-alpha.
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PMID:The role of lymphocytes in the neutrophil migration induced by ovalbumin in immunized rats. 754 May 91

We recently demonstrated that interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-6 and IL-8 can be found in nasal secretions from allergic rhinitis patients under artificial and natural conditions. By ELISA measurements, significantly elevated baseline levels for IL-1 beta, IL-6 and IL-8 were found in seasonal allergic compared to control subjects. Within the first 2 h after nasal allergen challenge, IL-1 beta and TNF are secreted, whereas IL-6 and IL-8 showed a slow increase over 6-8 h. All cytokine levels returned to baseline within 24 h after exposure. Repeated measurements at 4-week intervals in perennial allergic rhinitis subjects (n = 27) showed significant correlations between IL-1 and IL-8, IL-6 and IL-8 and IL-6 and the symptom score (visual analogue scale). The IL-1 receptor antagonist IL-1ra was found in great molar excess in the secretions and correlated significantly with IL-8, but not IL-1 beta. In an in vitro assay using fresh nasal mucosa of grass-pollen-allergic subjects, we were able to demonstrate a strong and rapid induction of E-selectin adhesion receptor expression on endothelial cells by allergen, IL-1 beta and TNF. The adhesion receptor expression was markedly inhibited by soluble IL-1 receptors, sTNF-R and IL-1ra. These data indicate a key role for inflammatory cytokines in the regulation of allergic inflammation.
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PMID:Proinflammatory cytokines: measurement in nasal secretion and induction of adhesion receptor expression. 754 54

To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall.
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PMID:Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. 754 86

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

The effect of cytokines, growth factors, mitogens, and bacterial products on nitric oxide (NO) generation by monolayers of small intestinal epithelial cells-6 (IEC-6) cells was evaluated. Subconfluent IEC-6 cells were maintained in DMEM containing 5% fetal calf serum and after 16-24 hr of incubation, the medium was replaced with fresh medium in the presence or absence of calcium ionophore (CaI), L-NAME, L-NNA, individual growth factors, cytokines, or mitogens. After 72 hr of culture, the media supernatant was collected and NO chi generation was determined. NO synthase activity was determined in sonicated supernatants of IEC-6 cells by [14C] arginine conversion to citrulline. NO chi generation in subconfluent cultures was greater than in fully confluent cultures, suggesting contact inhibition. NO chi generation by IEC-6 cells was significantly increased by CaI and inhibited by L-NAME and L-NNA. LPS, IL-1 beta, IL-2, IL-8, IFN-8, TFN-alpha, EGF, TGF-alpha, bFGF, and PHA significantly increased NO chi generation. NO synthase activity in IEC-6 cells (4.2 +/- 1.7 pmol/min/10(6) cells) was NADPH dependent. These results suggest that stimulation of NO chi generation by intestinal epithelial cells through cytokine bacterial products and mitogens may be one of the mechanisms responsible for their effects in the intestinal tract.
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PMID:NO chi generation by cultured small intestinal epithelial cells. 755 34


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