Biomedical subjects

E Vannier

Publications and source records attributed to E Vannier.

46 records · Page 3Linked to original sources

PubMed1991

Production of interleukin-1 receptor antagonist and interleukin-1 beta by peripheral blood mononuclear cells is differentially regulated.

We studied the relationship between the production of the 23-Kd interleukin-1 receptor antagonist (IL-1ra) and IL-1 beta in cultures of human peripheral blood mononuclear cells (PBMC) using a specific radioimmunoassay for IL-1ra that had a sensitivity of 166 +/- 11 pg/mL. PBMC cultured without human serum made little IL-1ra or IL-1 beta. In the presence of 1% AB serum, there was no increase in IL-1 beta (0.25 +/- 0.13 ng/mL) but IL-1ra production increased sevenfold to 3.4 +/- 0.5 ng/mL. IgG (2.5 to 100 micrograms/mL IgG) or granulocyte-macrophage colony-stimulating factor (GM-CSF) (1 to 100 ng/mL) had no significant effect on IL-1 beta production but increased IL-1ra production up to 18-fold (18.2 +/- 3.9 ng/mL). Using endotoxin as a stimulant, 82% +/- 2% of IL-1ra was secreted in comparison with 52% +/- 9% of IL-1 beta. Culture conditions of PBMC influenced the production of IL-1ra but not IL-1 beta. Rocking endotoxin-stimulated PBMC produced 75% less IL-1ra but the same amount of IL-1 beta when compared with PBMC cultured in stationary plastic tubes. Rocking IgG-or GM-CSF-stimulated PBMC also produced 75% to 80% less IL-1ra. GM-CSF or IL-1 beta at concentrations that elicited submaximal production of IL-1ra potentiated IgG-induced IL-1ra production. The production of IL-1ra and IL-1 beta are under differential regulation because serum, IgG, and GM-CSF were potent stimuli for the production of IL-1ra but not IL-1 beta, and the prevention of cell-cell contact of PBMC reduced IL-1ra but not IL-1 beta production.

Adult↗

PubMed1991

Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors.

Histamine and tumor necrosis factor alpha (TNF-alpha) can each contribute to the pathogenesis of allergic reactions and chronic inflammatory diseases. We now report the effect of histamine on gene expression and total cellular synthesis of TNF-alpha. Lipopolysaccharide (LPS)-induced synthesis of TNF-alpha in peripheral blood mononuclear cells (PBMC) from 18 healthy donors was suppressed by histamine concentrations from 10(-6) to 10(-4) M, levels comparable with those measured in tissues after mast cell degranulation. Histamine (10(-5) M) markedly suppressed LPS-induced synthesis of TNF-alpha in both unfractionated PBMC (83% inhibition, p less than 0.001) and monocytes purified by positive selection of LeuM3+ cells (62% inhibition, p less than 0.05). The suppressive effect of histamine on TNF-alpha synthesis did not require the presence of T cells. The histamine-mediated decrease in TNF-alpha synthesis was not affected by indomethacin, nor by diphenhydramine, an H1 receptor antagonist, but was reversed by cimetidine or ranitidine, H2 receptor antagonists, in a dose-dependent manner. Suppression of TNF-alpha synthesis by histamine is likely to be a transcriptional event, since histamine (10(-5) M) reduced TNF-alpha mRNA levels fourfold. These results suggest that histamine release from mast cells may paradoxically limit the extent of inflammatory and immune reactions by suppressing local cytokine synthesis in H2 receptor-bearing cells.

Cells, Cultured↗

PubMed1991

Lipopolysaccharide from Escherichia coli reduces antigen-induced bronchoconstriction in actively sensitized guinea pigs.

Bronchoconstriction (BC) is the main feature of anaphylaxis in the guinea pig. Since LPS induces lung inflammation and antigen-induced BC depends on the endogenous formation of histamine and arachidonate metabolites, we studied whether LPS might modulate antigen-induced BC. Guinea pigs were sensitized subcutaneously with 10 micrograms ovalbumin (OA) on days 0 and 14. LPS (100 micrograms/kg) was injected intravenously on day 21, and daily injections of LPS were continued before the antigenic challenge on day 22, 23, 24, or 25. Intratracheal injection of 100 micrograms OA induced an abrupt and reversible BC. Single or repetitive injections of LPS reduced BC. LPS is likely to reduce the OA-induced BC by affecting the histamine-dependent component of BC, since (a) LPS induced a partial degranulation of lung mast cells; (b) BC is reduced by mepyramine, an histamine receptor antagonist; (c) LPS did not affect BC in mepyramine-treated guinea pigs; (d) LPS reduced histamine release by OA-stimulated guinea pig lungs in vitro. Moreover, the in vitro OA-induced production of arachidonate metabolites was also reduced by LPS. The decreased formation of TXB2 was not only secondary to a reduced release of histamine, since LPS inhibited TXB2 formation in the presence of mepyramine. Finally, the FMLP-induced BC and mediator release were inhibited by LPS, whereas the platelet activating factor-induced pulmonary responses were not. Thus, the protective effect of LPS is not antigen-specific and does not result from a general desensitization. These studies indicate that a single dose of LPS reduces the antigen-induced BC by reducing histamine release from lung mast cells, although a decreased formation of eicosanoids may contribute to the protective effect of LPS.

Animals↗

PubMed1990

Production of cytokines by peripheral blood monocytes/macrophages infected with human immunodeficiency virus type 1 (HIV-1).

The study of monocyte/macrophage functions after human immunodeficiency virus type 1 (HIV-1) infection may help in understanding the pathogenesis of AIDS. The production of four cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF), by peripheral blood monocytes/macrophages was evaluated after in vitro infection with HIV-1. HIV-1 infection of these monocytes/macrophages did not result in release of any of these cytokines. Similarly, treatment of uninfected cells with purified recombinant HIV-1 envelope protein did not result in cytokine production. After stimulation with endotoxin or endotoxin plus interferon-gamma, HIV-1-infected monocytes/macrophages produced amounts of TNF alpha, IL-6, GM-CSF, and IL-1 beta comparable to that of uninfected cells. HIV-1 infection does not appear to induce or alter cytokine production by mononuclear phagocytes, which retain the capacity to produce these cytokines after endotoxin stimulation.

Biological Factors↗

PubMed1990

Human immunodeficiency virus does not induce interleukin-1, interleukin-6, or tumor necrosis factor in mononuclear cells.

The production of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) by fresh peripheral blood mononuclear cells was evaluated after exposure to human immunodeficiency virus (HIV) or purified recombinant HIV-1 envelope glycoprotein (rgp120). To exclude the role of contaminating endotoxin in this study, all media were subjected to ultrafiltration and reagents contained less than 25 pg of endotoxin per ml by Limulus assay. Under endotoxin-free conditions, no increases in IL-1 beta, IL-6, or TNF-alpha mRNA or protein were detectable in cell cultures exposed to HIV-1, HIV-2, or rgp120 (0.1 to 10 micrograms/ml), as compared with cytokine levels in mock-exposed cultures. However, concentrations of endotoxin (lipopolysaccharide) as low as 0.5 ng/ml induced significant production of mRNA and protein for these three cytokines. Preincubation of mononuclear cells with "shake" HIV-1 preparations and also mock-infected shake preparations prior to lipopolysaccharide stimulation resulted in a two- to threefold increase in IL-1 beta and TNF-alpha production. This priming effect was not observed with rgp120 (0.1 to 10 micrograms/ml) or standard HIV-1 or mock-infected supernatants, suggesting the presence of biologically active material independent of virus in the shake preparations. Our studies indicate that, in the absence of endotoxin, HIV-1, HIV-2, and HIV gp120 do not induce production of IL-1 beta, IL-6, or TNF-alpha by peripheral blood mononuclear cells.

Cells, Cultured↗

PubMed1989

Effects of ketoprofen and indomethacin on leukocyte migration in two models of pleurisy induced by carrageenan or zymosan-activated serum in rats.

The effect of nonsteroidal anti-inflammatory drugs on the in vivo leukocyte migration is not understood fully. In the present study, the effects of indomethacin and ketoprofen on the intrapleural leukocyte accumulation induced by carrageenan or zymosan-activated serum (ZAS) were investigated. Rats were given indomethacin or ketoprofen p.o. (1, 3 or 9 mg/kg) 1 hr before intrapleural injection of carrageenan (1 mg) or ZAS (0.5 ml). Pleural exudates were harvested 4 hr later. In each model of pleurisies, ketoprofen and indomethacin reduced the volume of exudate and leukocyte count in a dose-dependent manner but ketoprofen was more active than indomethacin. Ketoprofen and indomethacin had no effect on the protein concentration and the total complement activity of the exudates induced by carrageenan or ZAS. The spontaneous and directed migrations of leukocytes elicited by ZAS were unaffected by indomethacin and ketoprofen, whereas those of leukocytes elicited by carrageenan were more inhibited by ketoprofen than by indomethacin. These data demonstrate that ketoprofen is more active than indomethacin in reducing the in vivo leukocyte migration evoked by carrageenan or ZAS and suggest that the main effect of these two drugs is to reduce the increase in vascular permeability. Neutrophil chemotactic responsiveness and generation of chemotactic factors alone cannot explain the anti-inflammatory effect of ketoprofen and indomethacin.

Animals↗

PubMedDate not supplied

Resistance training alters cytokine gene expression in skeletal muscle of adults with type 2 diabetes.

Resistance training results in muscle hypertrophy and improves glycemic control in patients with type 2 diabetes. Whether resistance training modulates inflammation in muscles of diabetic patients remains unknown. We examined the expression of genes encoding the cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) as well as the pan-leukocyte marker CD18. Thirty men and women (67+/-7 years) were randomized to either 16 weeks of resistance training and usual diabetes care (EX) or to usual diabetes care only (CON). Muscle biopsies were obtained from the vastus lateralis muscle prior to the 16-week intervention, and 72 h following the maximal strength test post-intervention. Fiber cross-sectional area (CSA) was determined following ATPase staining. Cytokine and CD18 transcript levels were assessed by real-time PCR. Resistance training increased CSA of type I and II fibers (both P <0.05) and IL-1beta transcript levels (P = 0.05). TNF-alpha (P<0.05) and TGF-beta1 transcripts (P<0.05) increased over time in the EX group, but these increases did not differ from those in the CON group. In both groups, the increase in CD18 transcripts remained minimal. The two groups differ by the relationship between changes in CD18 and changes in cytokine transcripts, suggesting that resistance training affects the source of cytokines in muscle. Our studies establish that resistance training in older adults with type 2 diabetes results in muscle fiber hypertrophy, despite a greater accumulation of inflammatory cytokine transcripts in muscle.

Aged↗

PubMedDate not supplied

Computer-assisted ABR interpretation using the automatic construction of the latency-intensity curve.

In this paper, we present a new computerised technique for the automatic construction of the latency intensity curve (LI curve). We take a pattern recognition approach determined by a priori information. We use knowledge gained from the audiogram and from physiological considerations. Therefore, we consider all recordings at different intensities as well as results from the extraction of a single auditory brainstem response (ABR) at a given stimulus intensity. We tested our method successfully: it allows us to prevent misrecognition errors in response detection or in latency measurements. Automatic recognition of the waves and recognition by the ear, nose and throat (ENT) specialist coincided in at least 90 per cent of cases. For wave V, the average deviation between the response thresholds given by our automatic recognition algorithm and those given by the ENT specialist was 5 dB, and the average deviation of the latencies was 0.05 ms.

Auditory Threshold↗

PubMedDate not supplied

Comparison of granulocyte-macrophage colony stimulating factor and interleukin-1 production from human peripheral blood mononuclear cells as measured by specific radioimmunoassays.

Attention has focused on cytokine networks in which gene and protein expression of some cytokines is under the influence of other cytokines. In the present studies, we addressed the relationship between the synthesis of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-1 (IL-1) in human peripheral blood mononuclear cells (PBMC) stimulated with mitogens. Since bioassays for cytokines are sensitive to more than one of these factors, it was necessary to measure the amounts of IL-1 and GM-CSF independent of bioassays. A specific and sensitive (40 pg/ml) radioimmunoassay (RIA) was developed for human GM-CSF. The sensitivity of the RIA was greater when lysine residues were iodinated with Bolton-Hunter reagent than tyrosine residues using chloramine T. After stimulating PBMC with concanavalin A (Con A), the biological activity of GM-CSF was determined in bone marrow cultures and compared to immunoreactive GM-CSF; GM-CSF levels detected by bioassays and RIAs were highly correlated in two separate sets of experiments (r2 = 0.95 and 0.43). Incubation with Con A for 48 h induced more GM-CSF than stimulation by phytohemagglutinin (PHA) despite the fact that PHA stimulates large amounts of IL-1 alpha; indomethacin had no effect on Con A stimulated synthesis of GM-CSF or IL-1 alpha. In two separate studies, PBMC from 14 donors and a second group of 12 donors were incubated with Con A for 48 h and the total amount of immunoreactive IL-1 alpha and GM-CSF was determined in the same cell cultures. There was no correlation of the amount of either cytokines in these cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Effects of aging and cytokine blockade on inflammatory cachexia.

OBJECTIVE: To evaluate the role of aging and specific cytokine blockade in the etiology of cachexia caused by adjuvant arthritis (AA), a model of cytokine-associated cachexia. METHODS: AA was induced in Lewis rats using CFA. In Experiment 1, severity of AA and inflammatory cachexia was assessed in young (Y, age 2-6 months, n = 132) and old rats (O, age 18-22 months, n = 40). In Experiment 2, young rats were divided into 5 different intervention groups: Saline-injected (n = 66); CFA-injected (n = 78); CFA-injected and treated with IL-1 receptor antagonist (IL-1Ra, n = 18); CFA-injected and treated with soluble TNF receptor type I (sTNFrI, n = 27); and CFA-injected and treated with both IL-1Ra and sTNFrI (both treatments, n = 8). RESULTS: In Experiment 1, young Lewis rats developed more severe arthritis (mean joint score on day 21 = 5.1 +/- 0.3) compared to the old group (0.6 +/- 0.6, p < 0.0001). The young group with AA lost 2.1% of baseline total body weight loss compared to 13.8% total body weight gain in controls (p < 0.0001). In contrast, old rats injected with CFA lost as much weight (-11%) as age-matched saline injected controls (-13%, p > 0.05, n = 18, age 18-22 months). In Experiment 2, mean joint scores in rats treated with IL-1Ra, sTNFrI or both were higher then untreated rats injected with CFA (p < 0.0001). Despite this, rats given both IL-1Ra and sTNFrI lost less weight on day 16 (p < 0.01) and 21 (p < 0.002) than untreated rats or those rats treated with either IL-1Ra or sTNFrI. CONCLUSION: Lewis rats aged 2-6 months are more susceptible to developing AA than older rats (age range 18-22 months). Inhibition of both IL-1 and TNF is needed to mitigate AA-associated weight loss, and this effect is dissociated from the effect of such inhibition on joint inflammation.

Aging↗