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D A Vuitton

Publications and source records attributed to D A Vuitton.

At least 55 records · Page 3Linked to original sources

Alteration in the production of free oxygen radicals and proinflammatory cytokines by peritoneal and alveolar macrophages in old mice and immunomodulatory effect of RU 41740 administration. Part I: Effect of short and repetitive noise stress.

The aim of this study was to analyze the effects of stress on natural immunity in old mice, and the potential of an immunomodulating drug to correct stress-induced immune abnormalities. We analyzed both the alveolar (ALM) and peritoneal macrophage (PerM) oxidative responses and cytokine productions of TNF-alpha and IL-1alpha, in old mice after exposure to 3 days of noise stress, with and without treatment with RU 41740, an immunomodulating compound. Production of Free Oxygen Radicals (FOR) by ALM and PerM macrophages was evaluated using a luminol-dependent chemiluminescence method at the basal state and after stimulation. Serum corticosterone was also measured. Three groups of 22-24 month-old C57BL/6 mice were studied. Seven mice were treated with RU 41740 (10 mg kg(-1)) every day for 5 days and then exposed to sound stress (110 dB, 1000 Hz, for 3 nights). Ten mice were treated with saline, then submitted to a sham stress. Eight animals received neither treatment nor stress. There was no difference in corticosterone level between the three groups and between these groups and a control group nonstressed, noncannulated. After stimulation by fMetLeuPhe, production of FOR by ALM and PerM significantly increased after stress and returned to normal values after RU 41740 treatment (p < 0.001). The cytokine levels (TNF-alpha and IL-1alpha) decreased after stress and returned to normal levels after RU 41740 treatment. This study shows that, in aged mice, auditory stress is associated with modifications of macrophage functions which are different, depending on their localization and on the function under study. It confirms the immunomodulatory capacities of RU 41740 that was shown to counteract these effects of stress in elderly animals.

Adjuvants, Immunologic↗

In vivo treatment with recombinant IL-12 protects C57BL/6J mice against secondary alveolar echinococcosis.

Using an experimental model of hepatic Echinococcus multilocularis infection in C57BL/6J mice, intraperitoneal administration of 0.8 microgram of recombinant IL-12 to mice with an established infection was shown to reduce the parasite burden as soon as two weeks after the end of treatment. At that time, in vitro Echinococcus multilocularis-induced spleen T cell proliferative responses as well as IFN-gamma and IL-5 production were higher in IL-12 treated mice than in untreated mice. Administration of 0.8 microgram of IL-12 at the time of infection was shown to be without effect on the parasite establishment. However, this treatment greatly inhibited the subsequent metacestode development. Indeed, ten weeks after infection, it induced a complete healing in 37.5% of mice. At that time, the development of metastases was inhibited in 68.75% of IL-12-treated mice. This reduction of parasite burden was mainly associated with a strong proliferation of spleen cells to E. multilocularis antigen and with a high IFN-gamma production. Altogether, our results show that IL-12 is of crucial importance in inhibiting the larval growth after the metacestode establishment in the liver and suggest that this cytokine could be of potential value in the treatment of human alveolar echinococcosis.

Animals↗

Intestinal and systemic humoral immunological events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs.

The aim of the study was to investigate the systemic and, for the first time, the intestinal humoral events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. Thirty-one mice were divided into three groups; W-2, W-8 and control group. Each mouse of the W-2 and W-8 groups was orally infected with 1,500 E. multilocularis eggs, two weeks and eight weeks before sacrifice respectively. Control group mice received phosphate buffer saline. Measurement of anti-E. multilocularis and non-specific IgG, IgA and IgM, and of a transudation marker, albumin, were performed in serum and intestinal washings by a time-resolved immunofluorometric assay. These results were complemented by microscopic examination of the intestinal mucosa. This infection model is well-suited to the study of mucosal immunity during alveolar echinococcosis. It showed a major specific intestinal response in the early stage of the disease whereas the systemic response predominated later in the disease. Histopathological studies and calculation of the relative coefficient of excretion of Ig also confirmed that the presence of the parasite, even during a short period, was responsible for a local immunological and inflammatory response and for a change in mucosal permeability. Mucosal immunity could thus play a role in tolerance induction against E. multilocularis that could be a prerequisite for the subsequent development of the larvae in the liver, and for the occurrence of the parasitic disease, alveolar echinococcosis.

Animals↗

Echinococcus multilocularis infection in mice: in vivo treatment with a low dose of IFN-gamma decreases metacestode growth and liver fibrogenesis.

As no antiparasitic drug is definitively efficient in patients with alveolar echinococcosis, the effects of exogenous IFN-gamma on murine Echinococcus multilocularis infection were assessed with regards to the parasite burden, parasite-specific immune responses, and the urinary level of the collagen cross-link pyridinolines. They were analyzed after 3-week treatments with 1 or 5 micrograms of IFN-gamma per day twice a week. The treatment with 1 microgram transiently reduced the liver metacestode load, and the metastase weight as far as 6 weeks after the end of treatment. It slightly increased Th 1-type T cell responses and reduced the excretion of pyridinolines. These results should encourage further study to assess whether the decrease in liver fibrosis leads to an improvement of the efficacy of albendazole therapy. In contrast, the treatment with 5 micrograms increased the liver metacestode load and was less efficient than that with 1 microgram in decreasing pyridinoline excretion. These results incitate to follow up carefully patients with alveolar echinococcosis who are treated with IFN-gamma.

Amino Acids↗

Cross-reactivity between terrestrial snails (Helix species) and house-dust mite (Dermatophagoides pteronyssinus). I. In vivo study.

Clinical reports have suggested an unusual frequency in the number of patients with food allergy to snails who are also allergic to the house-dust mite (HDM). As allergy to HDM is one of the most frequent sensitizations in atopic patients of Western countries, evaluation of the relevance of the concomitant sensitization to Dermatophagoides pteronyssinus and to snails is an important consideration. To evaluate the responsibility of different snail components and of snail mites for inducing in vivo hypersensitivity in patients allergic to HDM, the in vivo reactivity of patients with clinical symptoms after ingestion of snails was assessed by skin prick tests with extracts and hemolymph from four different Helix species snails, and extracts from the snail parasitic mite, Riccardoella limacum. In addition, to obtain epidemiologic data on cosensitization to HDM and snails in allergic patients, the frequency of snail sensitization and its relationship to HDM sensitization were determined in a population of 169 allergic children. All patients allergic to snails had positive skin prick tests to the snail extracts and none to R. limacum extract. The number of positive skin reactions did not significantly differ whatever the species, snail part, or heating procedure used. The strongest reactions were obtained with Helix pomatia (Burgundy snail). Among the 169 prospectively tested children, 38 had a positive prick test to snail extracts; 79% of the snail-sensitized children had sensitization to HDM; and 31% of the children allergic to HDM were found to be sensitized to snails. These results show that snail components, and not the mite R. limacum, were responsible for the in vivo hypersensitivity. These snail components reacting in vivo are present in different parts of snails, including the hemolymph. One-third of the children allergic to HDM were sensitized to snails without any previous ingestion of snails: this observation suggests that HDM was the sensitizing agent and that the cross-reaction could be clinically relevant in countries where eating snails is common.

Adolescent↗

Cross-reactivity between terrestrial snails (Helix species) and house-dust mite (Dermatophagoides pteronyssinus). II. In vitro study.

Epidemiologic and in vitro data have shown that the association of house-dust mite (HDM) allergy and snail allergy in the same patients was due to cross-reactivity between HDM and snail allergenic components. However, the cross-reacting allergen(s) have not yet been identified. In vitro reactivity of seven patients' sera to the various extracts and hemolymph of four different Helix snail species was analyzed by IgE detection and immunodots and Western blots. Cross-reactivity between snails and Dermatophagoides pteronyssinus was assessed by immunodot and ELISA inhibition in two patients. Heterologous inhibition of the snail immunodot and ELISA was observed in one serum. Western blotting showed a specific binding on all four snail species extracts; molecular weights of snail allergens ranged from < 21 to 200 kDa. Marked individual differences were observed in the seven sera under study; most sera demonstrated IgE recognition of multiple bands, illustrating that no single allergen is responsible for cross-reactivity between snail and mite. These results confirm that cross-reactivity exists between snails of the Helix genus and HDM. This cross-reactivity, involving more than a single allergen, may be of clinical significance in atopic patients allergic to D. pteronyssinus. The identity of the cross-reacting allergens remains to be determined. Potential candidates include the thermostable minor allergens of D. pteronyssinus, tropomyosin and hemocyanin.

Animals↗

HLA and alveolar echinococcosis.

Evidence in animal intermediate hosts that susceptibility to larval infection with Echinococcus multilocularis is restricted to individual host factors prompted us to investigate the susceptibility markers in humans. Because antigens of the extracellular parasite E. multilocularis are possibly presented by MHC molecules in a restricted way, we speculated that MHC polymorphism may influence resistance of the host towards infection and course of disease. We studied HLA-A, -B, -DRB1, -DQB1 and -DPB1 polymorphism in 151 patients with alveolar echinococcosis. Patients with an observation period of more than 2 years were grouped according to the clinical follow-up into cured (no recurrence following surgery) patients and patients with regressive or progressive forms of disease during benzimidazole chemotherapy. By comparing phenotypic frequency between patients with alveolar echinococcosis and healthy controls, HLA-DRB1*11 was associated with a reduced risk for disease development (odds ratio=0.55, 95% confidence interval=0.34-0.88; P=0.01). HLA-DQB1*02 was more frequent in patients with progressive disease when compared with patients with regressive disease (54.3% vs 28.3%, P=0.02). The result suggests that HLA-DRB1*11 might confer protection against alveolar echinococcosis and that HLA-DQB1*02 may indicate a risk for progressive disease development. The findings may facilitate the search for immunodominant T-cell epitopes of E. multilocularis.

Animals↗

Lack of H-2 gene influence on mouse susceptibility to secondary alveolar echinococcosis.

To determine whether the development of hepatic Echinococcus multilocularis infection is influenced by major histocompatibility-linked genes, metacestode growth and host immune responses were compared in 4 C57BL/10 congenic murine strains of H-2b, H-2d, H-2k and H-2q haplotypes. Although the H-2q strain appeared slightly more resistant than the other strains, the 4 strains of mice developed comparable spleen cell proliferative response and Th1/Th2 cytokine production at 13 weeks p.i. A kinetic analysis, performed in 2 of these congenic strains, showed a similar pattern of parasite growth in these mice and failed to detect any significant difference in the production of parasite-specific IgM, IgG1 and IgG2, antibodies. Consequently, this study indicates that the control of secondary alveolar echinococcosis is not H-2 gene-linked.

Animals↗

Antibodies against Echinococcus multilocularis alkaline phosphatase as markers for the specific diagnosis and the serological monitoring of alveolar echinococcosis.

The immunological properties of the purified alkaline phosphatase (pAP) of Echinococcus multilocularis metacestodes have been investigated using alveolar echinococcosis (AE) patient sera in ELISA tests. A comparative study was done with EmC-Ag (crude antigen) and pAP-Ag (purified antigen). When the parasite purified enzyme pAP was used as antigen, the specificity of the ELISA was markedly increased since it reached 100% without any decrease of its sensitivity (100%). The serologic follow-up of AE patients was conducted during several months with these two antigens in three categories of patients: cured, stabilized and aggravated. There was a good correlation between clinical and serologic data when the pAP was used as antigen in ELISA tests. The anti-pAP antibodies titres did change more rapidly than anti-EmC antibodies titres when a recurrence occurred. Modifications of the anti-pAP antibodies levels were also observed during the patient's therapy: mebendazole, albendazole and Isoprinosine. These results suggest that pAP-Ag should be used for the diagnosis and the follow-up of AE patients.

Alkaline Phosphatase↗

Increased basal production of interleukin-10 by peripheral blood mononuclear cells in human alveolar echinococcosis.

The secretion of IL-10 by peripheral blood mononuclear cells (PBMC) and the expression of IL-10 mRNA in fractionated CD4+ and CD8+ lymphocyte subsets and non-B-non-T cells, with and without stimulation by the mitogen phytohemagglutinin-C (PHA-C) and specific Echinococcus multilocularis (E. multilocularis) antigens, were assessed in 7 patients with alveolar echinococcosis (AE) and 6 healthy subjects. Results of studies on IL-10 were compared to those on IFN-gamma, IL-4 and IL-5 in the same patients and control subjects. IL-10 production was significantly higher in patient PBMC-culture supernatants than in the control group supernatants, both at the basal level and after mitogen or specific E. multilocularis antigen stimulation. Both CD4+ and CD8+ lymphocyte populations and non-B-non-T cells of AE patients and controls expressed IL-10 mRNA. Semi-quantification of IL-10 mRNA revealed a significantly higher transcript level in unstimulated-CD8+ T cells from AE patients in comparison with CD8+ T cells of healthy donors. PBMC from patients produced very low levels of IL-4 but the production of IFN-gamma was not significantly depressed compared to the controls. PBMC, isolated from 4 AE patients and 4 control subjects stimulated with specific E. multilocularis antigens, secreted IL-5; IL-5 mRNA was only detected in the CD4+ lymphocyte subset. The secretion of IL-5 and the expression of IL-5 mRNA in healthy subjects could be due to the presence of non-specific mitogenic parasitic factors. This non-specific mitogenic activity of the parasite, besides inducing a high secretion of IL-10 in patients with evolutive AE, may contribute to the lack of host control of parasite growth and to the persistence of granulomatous lesions, due to the inhibition of an efficient Th1 immune response.

Adult↗

The WHO Informal Working Group on Echinococcosis. Coordinating Board of the WHO-IWGE.

WHO Informal Working Groups on Echinococcosis were founded in 1985 and for 10 years, under the leadership of Prof. J. Eckert (Zurich, Switzerland), they contributed much to facilitate exchanges between interested scientists working in their respective areas. In 1995, the Veterinary Public Health Unit, at WHO, decided to modify the functioning of the Groups and to transform them into a single Group. The Working Group brings together all the scientists involved in research on Echinococcosis whatever their specialty, field of interest, or type of Echinococcosis studied. The aim of the Group is to establish international networks on relevant, up-to-date and/or important problems in Echinococcosis on the basis of i) international cooperation, ii) high scientific standards, and iii) accurate methodology. A Coordinator is designated by WHO and has a 4-year term. He/she is assisted by a Coordinating Board. This board is also proposed for a 4-year term, so that it can be regularly renewed. It, thus, will give an opportunity for closer association with the life of the Working Group to many scientists; the coordinator for the next term will be chosen from among the participants so that a continuity of action is ensured. The current networks deal with: "Standardization of the ultra-sound classification of hydatid cysts" (coordinator: C. Mcpherson); "Long-term follow-up of patients treated with PAIR" (coordinator: C. Filice); "Standardization of the staging/classification of patients with Alveolar Echinococcosis" (coordinator: P. Kern); "Vaccination of sheep for the prevention of Echinococcosis: pilot trials" (coordinator: M. Lightowlers); "Standardization of immunological tools for the detection of Echinococcus coproantigens in carnivores" (coordinator: P.S. Craig); "Educational material for Echinococcosis prevention/control" (coordinator: L. Garcia); and "Methodology for the evaluation of the economical cost of Echinococcosis" (coordinator: G. Battelli). Two new networks are activated at the beginning of 1997: "Long-term evaluation of chemotherapy in cystic echinococcosis" (coordinators: T. Todorov, A. Teggi), and "Natural history of small single hydatid cysts" (coordinator: Z. Pawlowski). People interested in participating in these networks or wanting to create a network, can send their name, the description of their research team, and the part they plan to take in the proposed network. All the proposals are submitted to the Coordinating Board and to Dr Meslin (WHO "Research on and promotion of zoonotic disease surveillance and control" team). If the work undertaken by a network leads to a proposal for international classification/standardization, it is submitted for formal approval by WHO. It must be understood by everyone, however, that neither WHO nor the Informal Working Group can give any financial support for these networks; however they can help in advising participants about other sources of funding, and organizing meetings on given subjects. In conclusion, the WHO Informal Working Group on Echinococcosis will continue to play a major role in information exchange and in stimulating public interest in the field. It does not exclude any active group or scientist but tries to integrate them on the basis previously defined. The coordinator designated for the 1995-1999 period is Prof. Dominique A. Vuitton, WHO Collaborating Center for Prevention and Control of Human Echinococcosis, University Hospital, F-25030 Besançon, France (Tel. xx33 3 81665572, Fax xx33 3 81665570).

Animals↗