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Biomedical subjects

M Goldman

Publications and source records attributed to M Goldman.

At least 253 records · Page 14Linked to original sources
PubMed1995

T cells made deficient in interleukin-2 production by exposure to staphylococcal enterotoxin B in vivo are primed for interferon-gamma and interleukin-10 secretion.

The superantigen staphylococcal enterotoxin B (SEB) induces a defect in interleukin (IL)-2 production by T cells expressing specific T cell receptor V beta domains. The present study was undertaken to determine the capacity of T cells, made deficient in IL-2 production by exposure to SEB in vivo, to secrete interferon (IFN)-gamma and IL-10 and to induce pathology upon SEB rechallenge. For this purpose, BALB/c mice received two intraperitoneal injections of 100 micrograms SEB with a 48-h interval. First, we compared peak serum levels of IL-2, IFN-gamma and IL-10 after SEB rechallenge with those measured after a single SEB injection in control mice. The expected defect in IL-2 production in SEB-pretreated mice was associated with a major increase in IL-10 and IFN-gamma levels which were about fivefold higher than in controls. Experiments in mice depleted of CD4+ or CD8+ cells as well as studies in which purified T cell populations were rechallenged with SEB in vitro indicated that both CD4+ and CD8+ cells from SEB-pretreated mice were primed for IL-10 and IFN-gamma production. Furthermore, SEB-pretreated mice were sensitized to the toxic effects of the superantigen as indicated by a 30-70% lethality rate (vs. 0% in naive mice) within 48 h after SEB rechallenge. IFN-gamma was involved in the lethal syndrome as it could be prevented by injection of neutralizing anti-IFN-gamma monoclonal antibody. We conclude that SEB-reactive T cells made deficient for the production of IL-2 by exposure to SEB in vivo are primed for IFN-gamma and IL-10 production, and that IFN-gamma up-regulation is involved in the shock syndrome occurring upon SEB rechallenge.

Animals↗
PubMed1995

Interleukin-10 differentially regulates B7-1 (CD80) and B7-2 (CD86) expression on human peripheral blood dendritic cells.

Most of the immunosuppressive effects of interleukin-10 (IL-10) are related to functional inhibition of antigen-presenting cells (APC). Herein, we investigate the influence of recombinant (r)IL-10 on human dendritic cells (DC) purified from peripheral blood of healthy volunteers. First, we found that rIL-10 inhibited in a dose-dependent manner the proliferative responses as well as the production of IL-2 and interferon-gamma (IFN-gamma) in mixed lymphocyte reaction (MLR) between purified T cells and DC. This rIL-10 effect could be attributed to a direct effect on DC, as DC preincubated with rIL-10 were found to be deficient in the induction of alloreactive T cells even when anti-IL-10 neutralizing mAb was added at the time of MLR. Flow cytometric analysis indicated that rIL-10 did not modify the expression of ICAM-1 (CD54) and B7-1 (CD80), but decreased HLA-DR and B7-2 (CD86) expression at the DC surface. We conclude that the inhibitory effect of rIL-10 on primary alloreactive T cell responses involves down-regulation of class II MHC and B7-2 expression at the DC surface.

Antigens, CD↗
PubMed1995

Clinical and biological significance of interleukin-10 plasma levels in patients with septic shock.

Interleukin-10 is a potent macrophage-deactivating cytokine that inhibits lipopolysaccharide-induced tumor necrosis factor production. We determined the plasma levels of immunoreactive interleukin-10 in 16 patients with septic shock and in 11 patients with circulatory shock of nonseptic origin. In septic shock, interleukin-10 levels peaked during the first 24 h (median: 48 pg/ml) and decreased progressively till Day 5. In nonseptic shock, interleukin-10 plasma levels also increased during the first 24 h but to a lesser extent (median: 17 pg/ml). In septic shock patients, interleukin-10 plasma levels were positively correlated with tumor necrosis factor (r = 0.8, p = 0.01) and with parameters of shock severity including lactate levels (r = 0.56, p < 0.05) and correlated negatively with blood platelet counts (r = -0.65, p < 0.05). The decreased production of tumor necrosis factor-alpha and interleukin-6 after in vitro incubation of whole blood from septic shock patients with lipopolysaccharide was not influenced by in vitro neutralization of interleukin-10. We conclude that interleukin-10 is produced in patients with circulatory shock of septic and nonseptic origin and that the production of this anti-inflammatory cytokine during septic shock correlates positively with the intensity of the inflammatory response.

Adult↗
PubMed1995

Interleukin 10 prevents necrosis in murine experimental acute pancreatitis.

BACKGROUND/AIMS: Inflammatory events are believed to play an important role in the pathogenesis of acute pancreatitis. Interleukin 10 (IL-10) recently emerged as a major anti-inflammatory cytokine, inhibiting the secretion of proinflammatory cytokines by monocytes and/or macrophages. The potential protective role of IL-10 in a model of acute necrotizing pancreatitis in mice was tested. METHODS: Animals received two intraperitoneal injections of either 1000 U recombinant IL-10 or control supernatant before and during induction of acute pancreatitis with repeated cerulein injections (seven intraperitoneal injections of 50 micrograms/kg at hourly intervals). RESULTS: Systemic amylase and lipase release peaked 9 hours after the first cerulein injection. This peak was significantly reduced by IL-10 treatment. Histologically, edema and inflammation of the pancreas were observed in both groups, whereas necrosis was dramatically reduced in IL-10-treated animals. Serum tumor necrosis factor levels were undetectable in this model; reverse-transcriptase polymerase chain reaction analysis of resected pancreatic tissues performed at the time of maximal morphological alterations showed a dramatically decreased expression of tumor necrosis factor alpha messenger RNA after IL-10 treatment compared with control pancreatitis. CONCLUSIONS: IL-10 is able to decrease the severity of experimental acute pancreatitis, mainly by inhibiting the development of acinar necrosis. Inhibition of local tumor necrosis factor alpha might explain, at least in part, the protective effect of IL-10.

Acute Disease↗
PubMed1995

Spontaneous and cycloheximide-induced interleukin-10 mRNA expression in human mononuclear cells.

Interleukin-10 (IL-10) is known to be spontaneously produced by human peripheral blood mononuclear cells. In order to define the cell type in which IL-10 gene is spontaneously expressed we used the reverse polymerase chain reaction for IL-10 mRNA expression, which was also used to study the effects of cycloheximide (CHX). First, we found that IL-10 mRNA is spontaneously expressed in monocytes and B cells but not T cells from healthy donors, and second, we demonstrated that CHX superinduces IL-10 mRNA in monocytes and B cells. Experiments including nuclear run-on analyses established that the effects of CHX on IL-10 gene expression involve both gene transcription and mRNA stabilization.

B-Lymphocytes↗
PubMed1995

Plasma endotoxin and tumor necrosis factor-alpha in the hyperkinetic state of cirrhosis.

BACKGROUND/AIMS: The factors which trigger the hyperdynamic circulation in cirrhosis remain poorly defined. Plasma levels of the potent vasodilators endotoxin and tumor necrosis factor-alpha may be elevated in patients with cirrhosis, and therefore the potential role of these substance was assessed in the hyperkinetic circulation in cirrhosis. METHODS: Forty-nine patients in stable condition underwent systemic and hepatic hemodynamic measurements, and right atrial blood sampling for endotoxin and tumor necrosis factor-alpha assays. Patients were divided into three groups according to the severity of the disease: group 1 consisted of eight patients with normal liver or mild hepatic fibrosis, and groups 2 and 3 contained 17 and 24 patients with Child A and Child B or C cirrhosis, respectively. RESULTS: Systemic vascular resistance decreased and cardiac index increased from group 1 to 3: 1530 +/- 196 dyn.s.cm-5 to 990 +/- 72 dyn.s.cm-5 (mean +/- S.E.; p<0.05) and 3.1 +/- 0.3 l.min-1.m-2 to 4.2 +/- 0.2 l.min-2.m-2, respectively. Endotoxin was not detectable in any of the groups and tumor necrosis factor-alpha was increased in one patient from group 1, six from group 2 and six from group 3. Mean tumor necrosis factor-alpha levels were not different among the groups (10 +/- 5, 18 +/- 5 and 17 +/- 7 pg/ml in groups 1, 2 and 3, respectively). Systemic vascular resistance and cardiac index were not correlated to plasma tumor necrosis factor-alpha levels; patients with increased levels of this cytokine did not have worse hyperdynamic circulation in any of the groups. CONCLUSIONS: These results suggest that tumor necrosis factor-alpha and endotoxin do not play a role in the maintenance of the hyperkinetic state of cirrhosis.

Hemodynamics↗
PubMed1995

Lipopolysaccharide induces upregulation of neutral endopeptidase 24.11 on human neutrophils: involvement of the CD14 receptor.

1. As lipopolysaccharide is a major stimulator of neutrophil responses during Gram-negative bacterial infections, we studied its effect on the membrane expression of neutral endopeptidase 24.11/CD10 on neutrophils in a model of endotoxaemia in vitro. Lipopolysaccharide added to human whole-blood induced a marked and sustained CD10/neutral endopeptidase upregulation that was already detectable at 0.1 ng/ml and was maximal at a lipopolysaccharide concentration of 10 ng/ml. 2. We observed that neither tumour necrosis factor-alpha nor any newly synthesized protein was involved in the upregulation observed after 1 h incubation with 10 ng/ml lipopolysaccharide. 3. We further studied whether the lipopolysaccharide-induced CD10/neutral endopeptidase upregulation was mediated by lipopolysaccharide binding to the neutrophil CD14 receptor. Incubation of whole blood with an anti-CD14 monoclonal antibody before the addition of 0.1 ng/ml or 0.5 ng/ml lipopolysaccharide resulted in complete inhibition of CD10/neutral endopeptidase upregulation. In contrast, at a lipopolysaccharide concentration of 10 ng/ml, the anti-CD14 monoclonal antibody had an incomplete blocking effect. 4. The differential requirement for the CD14 receptor, depending on the lipopolysaccharide dose, was confirmed by the study of a patient suffering from paroxysmal nocturnal haemoglobinuria (in whom a complete defect in neutrophil CD14 expression was previously documented). 5. We finally confirmed these results using purified neutrophils, demonstrating that lipopolysaccharide-induced CD10/neutral endopeptidase upregulation depends on direct interaction with neutrophil CD14.

Antigens, CD↗
PubMed1995

Cryptococcal infection of the breast.

Deep fungal infections of the breast have been reported infrequently. These infections are usually discovered during an evaluation of a breast mass for neoplasia. We report a case of cryptococcal infection of the breast that presented as a mass lesion and was successfully treated with a combination of surgical excision and fluconazole and summarize eight additional cases from the literature. Because of the risk of disseminated and recurrent cryptococcal infection after surgical treatment alone, evaluation for disseminated disease and systemic antifungal therapy for cryptococcal mastitis are suggested.

Antifungal Agents↗
PubMed1995

High levels of interleukin-10 during the initial phase of fulminant meningococcal septic shock.

Interleukin (IL)-10 has an important antiinflammatory effect by inhibiting endotoxin-induced production of proinflammatory cytokines, such as tumor necrosis factor-alpha and IL-1. Since both cytokines are produced in massive amounts during fulminant meningococcal septic shock and are associated with severity of disease, IL-10 was measured in plasma samples of 25 consecutive children with fulminant meningococcal septic shock shortly after admittance to a pediatric intensive care unit. High levels of IL-10 (median, 6021 pg/mL; range, 137-24,600) were found in surviving patients (median, 1268 pg/mL; range, 137-24,600) and in those who died (median, 9915 pg/mL; range, 3996-14,100). IL-10 levels correlated weakly (r = .38; P = .055) with severity of disease as measured by the Glasgow meningococcal septicemia prognostic score. The findings indicate that IL-10 is produced in massive amounts in the initial phase of fulminant meningococcal septic shock.

Adolescent↗
PubMed1995

Differential effect of human immunodeficiency virus infection on the IgA and IgG antibody responses to pneumococcal vaccine.

The IgA, IgM, and IgG antibody responses to pneumococcal polysaccharide vaccine were analyzed in 35 asymptomatic or mildly symptomatic human immunodeficiency virus (HIV)-infected patients stratified according to their CD4 cell counts and in 12 healthy controls. Both the antibody titers in serum and saliva and the numbers of circulating antigen-specific antibody-producing cells (Elispot technique) were measured. At the peak of the antibody responses, HIV-infected patients mounted nearly normal IgG responses, while their IgM responses were significantly depressed, regardless of their CD4 cell counts. The IgA antibody response was decreased in patients with < 500 CD4 circulating cells/mm3. Most IgG antibodies belonged to the IgG2 subclass, and most IgA antibodies were dimeric IgA2 in both controls and patients. Anti-capsular pneumococcal polysaccharide IgG titers decreased much more rapidly in HIV-infected patients so that in all groups they were significantly lower than in controls 9 months after vaccination.

Adult↗
PubMed1995

The induction of human T cell unresponsiveness by soluble anti-CD3 mAb requires T cell activation.

In order to obtain an in vitro model of human T cell unresponsiveness induced by soluble anti-CD3 mAb in the presence of accessory cells, T cells purified from peripheral blood of healthy volunteers were cultured for 4 days with irradiated accessory cells and OKT3. After a 48 h resting period allowing TCR-CD3 complex re-expression, T cells were rechallenged with plastic-immobilized OKT3, and their proliferative response as well as their secretion of IL-2, IFN-gamma and IL-10 measured. Primary culture with OKT3 induced a state of unresponsiveness characterized by defective responses to OKT3 rechallenge but normal or enhanced responses to PMA and A23187 calcium ionophore, indicating a defect in the early steps of TCR-CD3-mediated signal transduction. Indeed, we found that unresponsive T cells displayed an impaired mobilization of intracellular calcium stores upon TCR-CD3 ligation. In order to determine whether the development of unresponsiveness depends on the initial T cell activation triggered by OKT3, we compared several versions of OKT3 differing in their ability to bind Fc receptors. We found that only the activating antibodies that bind Fc receptors on accessory cells induced T cell unresponsiveness. We conclude that human resting T cells can be rendered unresponsive by anti-CD3 mAb in soluble form provided that they trigger T cell activation.

Antigen-Presenting Cells↗