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Biomedical subjects

G Renoux

Publications and source records attributed to G Renoux.

At least 19 recordsLinked to original sources

Sodium diethyldithiocarbamate protects against the MPTP-induced inhibition of immune responses in mice.

The effects of 1-methyl-4-phenyl - 1,2,3,6-tetrahydropyridine (MPTP) on immune parameters, and the restorative influence of sodium diethyldithiocarbamate (DTC) or deprenyl were evaluated in mice. The concentrations of dopamine (DA), 3-methoxytyramine (3-MT), 3-4-dihydroxyphenyl acetic acid (DOPAC), and homovanillic acid (HVA), were concomitantly measured in the striatum. MPTP depressed T-cell responses. DTC restored these responses as well as the concentration of striatal DA. Deprenyl had no effect on the concentrations of DA and its metabolites, yet it modified the immune responses alike MPTP. The findings suggest a dopamine pathway could be involved in the brain-controlled immunostimulation afforded by DTC.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Interleukin-1 secretion by lipopolysaccharide-stimulated alveolar macrophages. Relationships to cell numbers--influence of smoking habits.

Interleukin-1 (IL-1) release by alveolar macrophages (AMs) from 29 patients with primary bronchogenic carcinoma, lung metastases, acute pneumonitis, and chronic infection was evaluated in response to a standard stimulus, lipopolysaccharide (LPS). The results were compared to those of AMs from normal smokers or nonsmokers (volunteers). AMs derived from healthy smokers secreted significantly more IL-1 than AMs from nonsmokers. In contrast, AMs from smokers affected with primary lung cancer have lost their capacity of secreting high levels of IL-1, whereas IL-1 secretion was high in nonsmokers with hematogenous metastases. AMs release high IL-1 levels in patients with acute bacterial infections. A significant correlation exists between numbers of AMs and IL-1 levels in normal individuals, a relationship which disappears in patients. These observations suggest that AMs in inflammatory lung disease, even discrete, have an increased capacity to secrete IL-1 on stimulation with LPS. They also suggest that an intrinsic dysfunction of AMs may accompany primary bronchogenic carcinoma. The influence of tobacco in modifying the functions of AMs is stressed.

Adult

Imuthiol influences on cytotoxic T cells and NK activity in +/+ and athymic nude BALB/c mice.

The effects of imuthiol (sodium ditiocarb, DTC) on the expression of cytotoxic responses (CTL) and natural killer (NK) activity were evaluated in aged and young euthymic mice, and in nu/nu BALB/c mice. Imuthiol generated CTL and concomitantly reduced NK activity in nu/nu mice, suggesting that the agent can generate T cells in athymic nude animals. Treatment for up to 4 months augmented spleen NK and CTL activities in young or aged euthymic mice, but the generation of CTL in old animals was increased by long-term treatments better than by a single injection. The capacity of imuthiol to activate specific and nonspecific cytotoxic functions in euthymic mice may contribute to enhancement of resistance in vivo against transformed cells after treatment with this agent.

Adjuvants, Immunologic

Immunopharmacology and immunotoxicity of zinc diethyldithiocarbamate.

Zinc is essential for the functions of the immune system, and sodium diethyldithiocarbamate (imuthiol) restores and regulates the numbers and activities of cells of the T-cell lineage. The combination of both elements was therefore tested for immune enhancement and immunotoxicity. The data presented herein show that the administration of zinc diethyldithiocarbamate was devoid of immunoenhancing influence on the responses to T-cell mitogens, and exerted a cytocidal effect on spleen lymphocytes.

Adjuvants, Immunologic

Brain neocortex and imuthiol regulate the expression of MHC antigens on mouse T lymphocytes.

The induction of T-cell responses involves the recognition of extrinsic antigens in association with antigens of the major histocompatibility complex (MHC). The present results demonstrate that the lateralized control exerted by the brain neocortex on T-cell activities extends to the expression of MHC antigens, yet differently on spleen or lymph node T cells. This study also shows that the neocortex influences the changes induced by an immunopotentiator, sodium diethyldithiocarbamate (imuthiol), on the MHC antigen content on mouse T cell-surface.

Animals

Asymmetrical involvement of the cerebral neocortex on the response to an immunopotentiator, sodium diethyldithiocarbamate.

We have previously shown that the neocortex in mice has a lateralized influence on the immune system. A partial left or bilateral neocortical lesion selectively decreases spleen T-cell numbers and function, natural killer and (NK) activity, but a right neocortical lesion do not affect NK activity, and increases T-cell numbers and T-cell-mediated events. Here we report that the immunopotentiating activity of sodium diethyldithiocarbamate (Imuthiol), a compound that selectively increases T-cell numbers and activities, is dependent on an intact neocortex. The effects of Imuthiol were examined in female C3H/HeJ mice 10 weeks after partial neocortical lesions. In animals with right or bilateral neocortical lesions, Imuthiol failed to increase the percentage of spleen T cells, did not influence the expression of class I MHC antigen on these cells, no longer induced the release in serum of specific T-cell-inducing factors, and failed to enhance T-cell-mediated events. In contrast, in animals with a left neocortical lesion, Imuthiol increased T-cell numbers and activities in a fashion that was comparable to that observed in unlesioned controls, but did not enhance NK activity. It is concluded that Imuthiol may affect immune responsiveness by acting directly on the neocortex and/or by interacting at subcortical levels with signals emitted by the neocortex. Moreover, this study reveals a major hemispheric asymmetry in the response to a drug.

Adjuvants, Immunologic

Early changes in immune parameters induced by an acute nonantigenic inflammation in mouse: influence of imuthiol.

Calcium pyrophosphate (CaPP)-induced pleurisy, may represent one of the simplest expressions of inflammation in that the irritant is a non-diffusible, non-antigenic and non-pyrogenic agent. Spleen or lymph node T or B cell numbers and activities, as well as NK activity, were modified at distance by CaPP-pleurisy. An intense increase in blood polymorphonuclear cells was also triggered by the inflammatory process. Treatment with imuthiol (sodium diethyldithiocarbamate), an agent known to be active on the T-cell lineage, restored towards control values the inflammatory response and tended to normalize white blood cell percentages altered by the inflammatory process. The findings suggest imuthiol could be employed as a virtually nontoxic and non-steroidal anti-inflammatory agent.

Animals

Disseminated aspergillosis in a patient with bronchiectasis. A 15-month clinical and immunological follow-up.

We report a case of disseminated aspergillosis involving both lung and brain in an adult female patient affected with bronchiectasis. Immunological follow-up was conducted before the clinical diagnosis and during the illness and revealed an excessively high helper-inducer/cytotoxic-suppressor (T4/T8) ratio. Peripheral granulocyte function was normal. A progressive reduction of lung and brain localizations was obtained with antifungal therapy and Imuthiol, an immunopotentiator which regulates the ratio of T-cell subsets. T4/T8 ratio returned to average values. The patient is alive 12 months after the diagnosis.

Adult

Genetic and epigenetic control of levamisole-induced immunostimulation.

Antibody responses to a T-cell dependent antigen, sheep red blood cells, were evaluated in mice of various inbred strains, treated or untreated, with levamisole. These responses appear to be under polygenic control, not associated with the H-2 complex, and modified by a Y-linked component and epigenetic factors revealed by aging. Strain, sex, age and the dose of levamisole all in influenced in an interrelated manner the activity of levamisole. Effects varied from inhibited to unchanged or increased antibody-forming cell numbers, without a direct relationship between the genetic regulation of levamisole effectiveness and a genotypic capacity to respond to the antigenic signal. Therefore, a complex relationship between host, antigen and immunopotentiator appears to be responsible for modifying the production of suppressor or helper influences. The present findings may serve as a warning against the uncritical use of levamisole.

Animals

Immunopotentiation and anabolism induced by sodium diethyldithiocarbamate.

Sodium diethyldithiocarbamate, DTC, enhances over a large range of doses macrophage listericidal capacity and T cell activities in terms of increased IgG-antibody forming spleen cells and delayed hypersensitivity levels. Such immunopotentiation is not associated with splenomegalia or increase in lymphocyte counts. Immunopotentiation requires a preexisting link between carbon disulfide and diethylamine, since both moieties were inactive if administered alone or on separate body sites. DTC demonstrates also an anabolic effect on mice emanciated by administering a B. melitensis cell-wall fraction. The role of DTC on hormonal production is discussed in relation to hormone-mediated action on T cell induction.

Adjuvants, Immunologic

Isoprinosine as an immunopotentiator.

Isoprinosine is a compound developed for antiviral use. The effects of isoprinosine on mouse responses to sheep red blood cells were studied over a wide range of doses, from 0.5 microgram/kg to 5 g/kg, i.p. administered at the time of i.v. immunization or as pretreatment for 7 days before antigenic stimulus. Low doses, 50 microgram/kg to 50 mg/kg, significantly increased the numbers of IgM- or IgG-spleen antibody-forming cells. Large doses, such as the LD50 (5 g/kg) or pretreatments where unable to impair mouse immune responsiveness. Isoprinosine (< 500 mg/kg/day) orally administered at time of or one day after immunization stimulated immune responses. In vitro addition of isoprinosine to spleen lymphocytes augmented PHA- or Con A-induced proliferation over a concentration range from 10 to 150 microgram/ml, whereas isoprinosine had no effect in the absence of mitogens. These data, and the lack of immunodepressing effect, suggest that there is a need for further evaluation of isoprinosine as an immunopotentiator.

Adjuvants, Immunologic

Differentiation and regulation of lymphocyte populations: evidence for immunopotentiator-induced T cell recruitment.

Isoprinosine, the p-acetaminobenzoic acid salt of inosine dimethylaminoisopropanol (1:3 molar ratio) and sodium diethyldithiocarbamate are two immumopotentiators which share an ability to induce in vivo acquisition of a specific T-cell marker by undifferentiated precursor lymphoid cells of healthy nu/nu mice, without affecting the B-cell lineage. Serum from treated nu/nu mice tested in dual assays, contains a selective inducer of prothymocytes.

Adjuvants, Immunologic

[Targets and mechanisms of levamisole-induced immunostimulation (author's transl)].

Levamisole modify the functions of neutrophils, of macrophages and of T-cells in normal, healthy men and animals. Hormone-like products are synthetized after levamisole administration, even in athymic mice, to recruit T cells from precommitted precursor cells and to activate mature T cells. Levamisole-induced immunostimulation is associated with activities of its sulphur moiety more than with cholinergic properties of the imidazole moiety. Levamisole activities are modulated by genetic and environmental factors and by the degree of antigenic stimulus. Immunostimulation by levamisole depends upon individual responsiveness. Practical usefulness of levamisole therapy will be optimal if acquired experimental findings are taken in account to determine the schedules of treatment.

Animals