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A Waage

Publications and source records attributed to A Waage.

At least 73 records · Page 4Linked to original sources
PubMed1995

Interleukin-1, interleukin-6 and tumor necrosis factor at delivery in preeclamptic disorders.

BACKGROUND: To examine if preeclamptic disorders lead to altered concentrations of tumor necrosis factor, interleukin-1 and interleukin-6 at delivery compared to normal pregnancy. METHODS: Amniotic fluid, placenta, maternal and cord serum were collected at delivery by cesarean section or spontaneous labor. Samples were retrieved from 53 women with normal pregnancy, 54 with preeclamptic disorders and 15 who delivered a small for gestational neonate of unknown cause. Cytokines were measured by bioassays. Statistics were performed with nonparametric tests. RESULTS: Interleukin-1 in amniotic fluid tended to be lower with preeclamptic disorders than in normal pregnancy irrespective of labor. There was an increase in amniotic fluid tumor necrosis factor, interleukin-1 and interleukin-6 with onset of labor in preeclamptic disorders just as in normal pregnancy. There was a similar increase in interleukin-6 in cord and maternal serum in the same groups, even if concentration of interleukin-6 in cord serum in labor of preeclamptic disorders was lower than in normal pregnancy. CONCLUSIONS: No major differences were seen in concentrations of interleukin-1, interleukin-6 and tumor necrosis factor in amniotic fluid, placenta, maternal or cord serum at delivery with preeclamptic disorders compared to normal pregnancy.

Adult↗
PubMed1995

Antigen presentation by human fetal astrocytes with the cooperative effect of microglia or the microglial-derived cytokine IL-1.

Antigen presentation by endogenous glial cells is postulated to regulate reactivity of immune cells that gain entry into the CNS. We have previously observed, using a mixed lymphocyte reaction (MLR) system, that adult human-derived microglia can function as antigen-presenting cells (APC) for immediately ex vivo CD4+ T cells in a primary MLR (1 degree MLR) whereas astrocytes could not. We have now found that fetal human astrocytes can support CD4+ T cell proliferation in the presence of exogenous human recombinant (r) IL-2, and that astrocytes can support the continued proliferation of CD4+ T cells previously sensitized to sister astrocyte cultures in a secondary MLR. Additionally, adult human microglia, seeded into the nonpriming astrocyte: CD4+ T cell cocultures at non-T cell-stimulatory concentrations of 1000-5000 microglial cells per well, could reverse the inability of astrocytes to present antigen in the primary MLR. To examine the cellular basis for the inability of human astrocytes to function as APCs in the primary MLR, astrocyte- and microglial-enriched populations were established from human embryonic and adult brain, respectively, and analyzed for their ability to synthesize cytokines potentially relevant as accessory signals in the MLR. Microglia had transcript as determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) and protein as determined by bioassay for IL-1 alpha, IL-6, and TNF alpha. Human fetal astrocytes had transcript for IL-6 but not for IL-1 alpha or TNF alpha under basal culture conditions and following IFN gamma stimulation. The addition of human rIL-1 from 1-50 U/ml could reverse the inability of astrocytes to present antigen in the primary MLR. These studies demonstrate that although in vitro highly enriched cultures of astrocytes absent of microglia cannot present antigen to immediately ex vivo blood-derived CD4+ T cells in the MLR, in situ, with the cooperative help of microglia-derived cytokines or accessory surface molecules, astrocytes may function as central nervous system APCs.

Adult↗
PubMed1994

Activation of adult human derived microglia by myelin phagocytosis in vitro.

The present study was designed to determine the extent to which cultured glial cells phagocytose normal central nervous system (CNS) myelin and CNS myelin opsonized with serum or purified antibody against myelin basic protein (MBP). Glial cells studied were mixed cultures (consisting of astrocytes, microglia, and oligodendrocytes) and enriched microglia established from adult human brain specimens and enriched astrocytes from fetal human brain. A human monocytic cell line, THP-1, was included as a control. Uptake of 125I-labelled myelin was followed over a 24 hr time period. An assay of oxidative burst (30 min) and cytokine bioassays measuring IL-1, IL-6, and tumor necrosis factor (TNF) production (6-48 hr) were used to investigate short- and long-term activation of phagocytosing cells. Maximum myelin uptake by phagocytosing glial cells occurred within 12-24 hr following myelin incubation. Opsonization of myelin prior to the phagocytosis assay resulted in greater myelin uptake by mixed glial cell cultures, microglia, and THP-1 cells over that of nontreated myelin. The magnitude of myelin phagocytosis by astrocytes was considerably lower than microglia and THP-1, and was not affected by myelin opsonization. Within 30 min of myelin phagocytosis, microglia and THP-1 cells underwent oxidative burst; opsonization of myelin by purified anti-MBP IgG and heat-inactivated serum enhanced the microglial oxidative burst activity. Production of IL-1, TNF, and most markedly IL-6 by microglia was increased following 12-24 hr of myelin ingestion. Our data demonstrate that myelin phagocytosis by adult human-derived microglia occurs in vitro, is augmented when myelin is opsonized, and results in the activation of microglia as assessed by oxidative burst and cytokine production.

Adult↗
PubMed1994

Interleukin 8 in serum in granulocytopenic patients with infections.

Serum levels of interleukin 8 (IL-8) were examined in eight patients with acute myeloid leukaemia during 16 courses of chemotherapy. The patients experienced 14 episodes of fever which occurred in periods with granulocyte counts < 0.5 x 10(9)/l. Febrile episodes were classified as bacteriologically defined infection (n = 6), clinically defined infection (n = 2), and unexplained fever (n = 6). IL-8 was detected in 18/25 (72%), 2/3 (67%) and 3/7 (43%) of the serum samples in the respective groups. In contrast, IL-8 was detected in 22/90 (24%) of the samples taken when no fever was present (P < 0.00003 versus bacteriologically defined infection). The median concentration of IL-8 in samples taken during febrile episodes was 194 ng/ml (range 0-6358 ng/ml) and 0 (range 0-5392 ng/ml) on days without fever (not significant). In three patients with infections caused by, respectively, Streptococcus sanguis, Acinetobacter calcoanitratus and Candida albicans, IL-8 rose to a peak levels and declined during recovery. We conclude that IL-I is released systemically during infections with gram-positive and gram-negative bacteria and Candida albicans in patients with acute myeloid leukaemia and peripheral granulocytopenia due to chemotherapy. However, IL-8 can also be detected when no sign of infection is present.

Acute Disease↗
PubMed1994

TNF and IL-6 are potent growth factors for OH-2, a novel human myeloma cell line.

A novel human myeloma cell line, OH-2, was established from pleural fluid of a myeloma patient in end stage of the disease. Effects of cytokines on proliferation were analyzed by measuring uptake of 3H-thymidine. Cell surface antigens were detected by flow cytometry. The cell line is dependent on IL-6 for growth and proliferates in response to TNF. There is synergy between the stimulatory response of TNF and IL-6. The cells express both the p55 and p75 TNF receptors. Neutralizing anti-IL-6 did not inhibit TNF-mediated proliferation, showing that TNF acts through a pathway that is independent of IL-6. TNF was more potent than IL-6 in stimulating the growth of primary myeloma cultures (> 99% pure) from the same patient (OH-2-PC), indicating that TNF in selected myeloma patients has a growth-promoting effect equal to IL-6. OH-2 cells produce and secrete monoclonal IgG-kappa.

Antigens, CD↗
PubMed1994

TNF receptors in chronic lymphocytic leukemia.

Two transmembrane receptors for tumor necrosis factor (TNF) with different molecular weight, 55 kD (p55) and 75 kD (p75), have been identified. In addition, the extracellular part of both receptors are shedded by proteolytic cleavage and exist as soluble receptors which bind to TNF in plasma and other biological fluids. Normal B cells produce TNF and express TNF receptors (R), mainly p75, upon stimulation. TNF costimulates DNA synthesis via the p75 receptor in normal B cells. The B cells from patients with chronic lymphocytic leukemia (CLL) produce TNF and have the capacity to express both receptor types. Also in malignant B cells the p75 receptor is dominant. TNF induce DNA synthesis in CLL cells via both receptors. CLL patients have elevated serum levels of soluble (s) TNFR and this is more pronounced in advanced disease. In conclusion, there is considerable support for TNF as an autocrine growth factor in CLL. However, the net effect of TNF is determined by the quantitative relationship between TNFR on the cell surface, TNF in plasma and sTNFR in plasma, and the affinities between TNF-p55 and TNF-p75. Due to increasing serum levels of sTNFR the significance of TNF as a growth factor is probably less important in advanced disease.

B-Lymphocytes↗
PubMed1994

Acute leukemia in middle Norway 1984-88.

One hundred and eight adult patients with acute leukemia were diagnosed in the middle Norwegian health region during the 5-year period 1984-88, giving an incidence rate of 4.6/100,000 per year. Nine patients had acute lymphoblastic leukemia (ALL), 93 acute myeloid leukemia (AML) and 6 patients acute leukemia without definite sub-classification. The median age of AML patients was 66 years. Thirty-five patients (median age 78 years) were found non-suitable for cytotoxic drugs, while 58 AML patients (median age 57 years) were given aplasia-inducing drug combinations according to one of three treatment programs depending on the time of diagnosis and age, in order to induce remission. Six patients were given oral drugs or low dose ara-C. All patients were followed until death or for an observation time of more than 5 years (median 7 years). The overall long term survival was found to be 12/108 for all acute leukemias, 8/93 for AML patients and 4/9 for ALL patients. For the AML patients given intravenous aplasia-inducing drugs the remission rate was 0.65, the median remission duration 12.2 months and the 5-year survival rate 0.19. For 31 AML patients, (median age 41 years), started on an intensive chemotherapy program, the 5-year survival rate was 0.32 and the relapse-free 5-year survival rate for the 22 patients entering complete remission was also 0.32.

Acute Disease↗
PubMed1994

Effects of a combined drug regimen on tumour necrosis factor and plasma kallikrein activity in experimental endotoxaemia.

OBJECTIVE: To clarify the relationship between changes in haemodynamics, liberation of tumour necrosis factor and generation of plasma kallikrein, and to see if treatment with a combination of drugs was successful in preventing activation of tumour necrosis factor and plasma kallikrein in experimental endotoxic shock. DESIGN: Controlled study. MATERIAL: 22 juvenile pigs. INTERVENTIONS: 15 animals received 0.01 mg/kg endotoxin infusion, the rest being given the same volume of saline. 10 received no treatment, and 5 were given a combination of methylprednisolone, naloxone, ketanserin, promethazine, C1 esterase inhibitor, antithrombin III and aprotinin. MAIN OUTCOME MEASURES: Assessment of the liberation of tumour necrosis factor, generation of plasma kallikrein, and haemodynamic and cellular effects of endotoxaemia. RESULTS: There was a linear statistical relationship between decreases in cardiac output and increases in packed cell volume, and between increases in packed cell volume and plasma kallikrein activity. The combination treatment totally blocked all the effects of the infusion of endotoxin. CONCLUSION: Endotoxin affects several mediators, but combination treatment can prevent some of these effects.

Animals↗
PubMed1993

Tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy.

OBJECTIVE: Our purpose was to investigate the cytokines, tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy and labor. STUDY DESIGN: Bioassays were used to measure these factors in extraembryonic coelomic fluid, amniotic fluid, placenta, and maternal and cord serum. RESULTS: Little or no tumor necrosis factor, interleukin-1, or interleukin-6 was found in coelomic fluid or amniotic fluid in the first trimester. Interleukin-6 appeared in second-trimester amniotic fluid. At term tumor necrosis factor was present (median 17 pg/ml) and increased with the onset of labor (median 58 pg/ml), as did interleukin-1 (median 188 to 680 pg/ml) and interleukin-6 (median 399 to 4800 pg/ml). Maternal serum interleukin-6 increased during pregnancy with a further increment with the onset of labor. Cord interleukin-6 also increased with labor but at a lower level. CONCLUSION: The cytokines tumor necrosis factor, interleukin-1, and interleukin-6 may play a role in the onset of normal labor.

Amniotic Fluid↗
PubMed1993

Interleukin-8 in serum and cerebrospinal fluid from patients with meningococcal disease.

To evaluate the role of interleukin (IL)-8 in meningococcal disease, a solid-phase double-ligand ELISA was used to quantitate IL-8 in sera and cerebrospinal fluid (CSF) from patients with meningococcal meningitis, bacteremia, or both with or without septic shock. IL-8 was demonstrated in sera from 28 of 62 patients; levels were significantly higher in patients with septic shock without meningitis (median, 36.1 ng/mL) than in patients with other manifestations (median, < 0.02 ng/mL), and 4 of 5 patients who died had high levels. IL-8 was detected in all 27 CSF samples. Serum IL-8 levels correlated highly significantly with those of IL-6 (r = .83) and tumor necrosis factor (TNF; r = .64), while the correlations between corresponding CSF levels were less pronounced (r = .43 and r = .38, respectively) but still significant. Serum IL-8 levels were highest in patients with a symptom history < 12 h. The elimination rate of IL-8 from serum varied and was similar to that of IL-6 and TNF. IL-8 appears to participate in the complex cytokine network during the initial phase of systemic meningococcal infections.

Adolescent↗
PubMed1993

Effects of stem cell factor and granulocyte colony-stimulating factor on granulocyte recovery and Candida albicans infection in granulocytopenic mice.

The combined action of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) on granulocyte recovery and infection with Candida albicans was studied. In mice rendered granulocytopenic with 200 mg/kg cyclophosphamide, daily coinjection of SCF (100 micrograms/kg) and G-CSF (10 micrograms/kg) for 5 days synergistically stimulated granulocyte recovery compared with either factor alone. Growth of C. albicans in the kidneys of granulocytopenic mice with experimental C. albicans infection was reduced by the combined regimen to 25% of that in vehicle-treated controls (P = .018), whereas either factor administered alone in the same doses had no effect. The combined regimen also significantly protected against lethal infection with C. albicans (P < .01). Either factor administered alone in the same doses had no effect on lethality compared with vehicle-treated controls. The combination of SCF and G-CSF may be useful in the treatment of infections with C. albicans in the granulocytopenic host.

Agranulocytosis↗
PubMed1993

Lack of IL-1 secretion from human myeloma cells highly purified by immunomagnetic separation.

This paper describes a method for purification of human myeloma cells. Mononuclear cells from six bone marrow samples and one pleural fluid sample from multiple myeloma patients were incubated with B-B4, a monoclonal antibody that is specific for plasma cells, and the B-B4+ cells were isolated using monosized magnetic beads coated with sheep anti-mouse Ig. With this positive selection method it was possible to achieve primary cultures with more than 99% myeloma cells. The average viability of these cultures was 81%. The B-B4 antibody did not alter proliferation or cytokine production of the myeloma cell lines U-266 and JJN-3. The B-B4+ myeloma cultures did not produce IL-1 and made only small amounts of IL-6 (< 93 pg/ml), whereas the cells remaining after extraction of the B-B4+ cells produced IL-1 (89-350 pg/ml) and large amounts of IL-6 (520-17,000 pg/ml). This indicates that the B-B4+ myeloma cells are not directly responsible for the overproduction of these cytokines in multiple myeloma. This separation technique gave higher purity of myeloma cells than has been previously reported for any negative selection method and is recommended when high culture purity is of critical interest.

Adult↗
PubMed1993

Cytokine mediators of septic infections in the normal and granulocytopenic host.

Cytokines presently known to be involved in systemic bacterial infection are tumour-necrosis factor (TNF), interleukin (IL)-1, IL-6, IL-8 and interferon-gamma (IFN-gamma) and the counterregulatory molecules soluble TNF receptor (sTNFR) and IL-1 receptor antagonist (IL-1 Ra). In animal models TNF, IL-1 and IFN-gamma mediate organ damage, low blood pressure and fatality, whereas IL-6 is involved in infection-related manifestations, like the production of acute-phase protein and fever, and IL-8 is chemotactic to granulocytes. TNF and IL-1 increase expression of adhesion molecules on endothelial cells and influence a number of components of the haemostatic system in favour of coagulation. The presence of cytokines in the circulation is characterized by sequential releases of TNF, IL-1 and IL-6/IL-8; however, many variations of this pattern exist during human infection. In experiments as well as in human infection TNF, IL-1, IL-6, IL-8 and IFN-gamma have been detected, and levels of TNF, IL-6 and IL-8 have been found to be associated with the severity of the disease. Collectively, TNF, IL-1 and IFN-gamma emerge as mediators of systemic infection and septic shock whereas IL-6 and IL-8 are related to other manifestations of infection. Counteracting molecules like sTNFR are released after somewhat of a delay following TNF and IL-1Ra is released concomitantly with IL-1. Probably these factors modulate the cytokine effect although their true potency in natural infection has yet to be clarified. In granulocytopenic infections TNF, IL-1, IL-6 and IL-8 can be detected in serum, and levels of TNF and IL-6 are even higher than in the normal situation in experimental animals. Antibodies to TNF inhibit bacteria-induced fatality in granulocytopenic mice. Altogether, few data related to the granulocytopenic situation are available. However, it is reasonable to believe that the altered development of granulocytopenic infections is due to changes in the cellular constitution and not to changes in cytokine production.

Agranulocytosis↗
PubMed1992

p55 and p75 tumor necrosis factor receptors in patients with chronic lymphocytic leukemia.

We studied the expression of the two tumor necrosis factor (TNF) receptors, p55 and p75, on B cells from patients with chronic lymphocytic leukemia (CLL), and the presence of soluble TNF receptors in serum. Expression of membrane-associated receptors was quantified by double labeling of peripheral blood mononuclear cells (PBMC) with monoclonal antibodies against CD19 and p55/p75 TNF receptors and flow cytometry. A high fraction of the CD19+ cells expressed the p55 receptor (44% +/- 34% [SD]) and p75 receptor (61% +/- 31%). In healthy controls, 0% to 1% of the CD19+ cells expressed the p55 receptor and 0% to 10% expressed the p75 receptor. Incubation of CD19+ cells with 10 ng/mL of TNF increased the incorporation of thymidine in 11 patients tested, and this was decreased to 65% (P < .05) by antibodies to the p55 receptor or the p75 receptor, and to 35% +/- 7% (P < .001) when both antibodies were combined. With an enzyme-linked immunoassay, we measured soluble TNF receptors in serum from CLL patients. The mean level of p55 receptors was increased to 12.9 +/- 8.9 ng/mL (P < .000001 v normal). The mean level of p75 receptors was increased to 13 +/- 24 ng/mL (P = .01 v normal). The membrane expression of the two receptors was positively correlated (r +/- 97, P < .01); however, there was no correlation between membrane expression and serum concentration of either receptor. Autologous serum containing high levels of soluble TNF receptors inhibited TNF-induced proliferation of CD19+ cells. In conclusion, we have demonstrated that neoplastic cells from patients with CLL have increased expression of p55 and p75 TNF receptors, and that both receptors mediate signal to proliferation. Furthermore, serum from CLL patients has elevated levels of soluble TNF receptors, which may counteract the proliferative effect of TNF.

Antibodies, Monoclonal↗