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Biomedical subjects

G Renoux

Publications and source records attributed to G Renoux.

At least 19 recordsLinked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

Immunologic indices in myelodysplastic syndromes.

Immunocompetence was evaluated in 36 untreated and noninfected patients affected with myelodysplastic syndromes (MDS). T-cell number and activity were evaluated by counts of total T-cells and T-lymphocyte subsets, and by measure of DNA synthesis in response to phytohemagglutinin and Concanavalin A. B-cells were evaluated as surface immunoglobulin- (SIg+) bearing cells and by serum immunoglobulin levels. Granulocyte activities were evaluated by responses to chemotaxis and to nitroblue tetrazolium test. Complement activity was measured by classic hemolytic complement assay. In addition, circulating immune complexes were detected in serum. MDS were associated with a significant decrease in the absolute numbers of total T (E-rosetting and T3+) cells, T4+, and T8+ cells and a dramatic decrease of the responses to Concanavalin A. An impairment of either chemotaxis or of nitroblue tetrazolium (NBT) test was frequently encountered. An increase in the levels of IgG or IgA was also a frequent feature. The findings reveal that all patients with a high degree of T-cell impairment have refractory anemia associated with an excess of medullary blast cells. All in all, the data suggest that the counts of the absolute number of cells bearing the T3 and T8 phenotypes could be of prognostic value: the higher the number, the better the patient's survival.

Adult↗
PubMed1988

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↗
PubMed1988

The cortex regulates the immune system and the activities of a T-cell specific immunopotentiator.

Evidence has accumulated to demonstrate important bidirectional communications between the nervous and immune systems. The anatomic pathways of communication include the commitment of different midbrain areas to regulation of immunologic functions. Neuropeptides appear as critical mediators of neuroregulation of function of diverse immunocompetent cells. Biochemicals secreted by immunocompetent cells mediate the effects of the immune system on the nervous system. We provide suggestive evidence that the above summarized effects are under a lateralized control of the neocortex. Furthermore, the neocortex has a lateralized influence on the immunopotentiating effects of sodium diethyl dithiocarbamate (imuthiol), which compound selectively increases T-cell numbers and activities, and acts on cholaminergic pathways. Thus, a major hemispheric asymmetry in the response to a drug is revealed. These results point to an important influence of neocortex on number and function of immunocompetent cells, which role can be modified by pharmacologic agents.

Animals↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1986

The ten commandments for immunotherapeutic drugs at the example of sulfur-containing agents.

Immunotherapeutic agents (IMT) are intended to restore or reequilibrate a faltering immune system. Levamisole was the first chemically defined IMT endowed with immunomodulatory effects. In order to clarify the mechanisms of its ambivalent activities, thiocompounds were tested for their ability to modify immune responses. All thiomidazoles are immunomodulatory drugs which dose-dependent effectiveness is related with the cholinergic-like influence of the imidazole moiety. The findings suggest also a relationship among thiodrugs between chemical structure and influence on the immune system. These studies lead to the development of sodium diethyldithiocarbamate (Imuthiol), as a non-toxic immunostimulant agent, specifically active on the T-cell lineage. Our studies unequivocally put forth on the specific requirements that are essential to characterize a potential IMT prior to clinical release: in vivo activities no immunosuppression through prolonged administration no antigenicity or hapten-like activity no carcinogenicity or tumor-promoting influence experimental route of administration related to that in humans assays in various animal strains pharmacokinetics chemical characterization known toxicities, teratogenesis, and mutagenesis assays on models of cancer, autoimmune diseases, immunodeficiencies, and infections. The results will allow to determine a range of doses, and predict most direct and secondary effects. They will also specify whether the agent is an adjuvant, a reticulostimulant, an immunomodulatory, an immunostimulatory, an immunorestorative, or an immunoregulating drug. Clinicians will therefore be provided with the data which are essential to perform useful clinical testing.

Adjuvants, Immunologic↗
PubMed1986

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↗
PubMed1986

Fate and distribution of radioactive sodium diethyldithiocarbamate (Imuthiol) in the mouse.

The distribution of 35S in mouse tissues has been investigated by radioactivity counts and by autoradiography after the intravenous injection of 35S-labeled imuthiol (sodium diethyldithiocarbamate). Radioactive Imuthiol is selectively localized on liver, thymus and brain neocortex, most likely as the methyl ester, within minutes after dosing. Lung or white brain matter did not fix the labeled thiol. Blood, kidney and guts show rapid elimination patterns, and can be considered as passage organs which did not fix Imuthiol. The findings are consistent with the immunopharmacological data which demonstrate that Imuthiol exerts its T-cell recruiting and activating influence through a multi-step pathway involving the brain neocortex, the thymus and the liver.

Animals↗
PubMed1986

Influences of sodium diethyldithiocarbamate, DTC (imuthiolR) on T cell defective responses of aged BALB/c mice.

The effect of chronic imuthiol treatment, 25 mg/kg weekly for 4 months initiated at the age of 12 months, on T-cell functions of aged female BALB/c mice was investigated. Imuthiol restored to normal value the impaired response to Concanavalin A (Con A) and enhanced the proliferative response to phytohemagglutinin (PHA). Impaired cytotoxic T-cell activity (CTL), was restored near to the value of young controls by imuthiol. Serum thymic factor (FTS) levels in serum of treated aged animals outpassed those of untreated young mice. Delayed-type hypersensitivity (DTH) reaction to oxazolone was increased. In contrast, the graft-vs-host (GVH) mortality induced by injecting H-2 histoincompatible cells to irradiated recipients, which GVH was impaired by aging, was not significantly modified by imuthiol. The excessive cytotoxicity for chicken red cells of macrophages (ADCC) from aged mice was reduced, as well as macrophage cytotoxicity for tumor cells. Natural killer cell activity remained unchanged. This finding confirms that imuthiol enhanced effectively T cell-dependent responses but the data on GVH reaction suggest that its effects are under a complex mode of action. Restoration of a normal production of FTS may be one mechanism by which imuthiol acts on the reinduction of the T-cell differentiating pathway in aged mice.

Aging↗
PubMed1986

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↗
PubMed1986

Characterization of immunotherapeutic agents: the example of imuthiol.

Immunotherapeutic (IMT) agents are intended to restore or reequilibrate a faltering immune system. These aims will be attained provided the agent fulfills minimum requirements: in vivo defined activities; lack of suppressive, sensitizing, or autoimmunity-inducing influence; no immunotoxicity and carcinogenicity. Known chemical structure, analytical procedure, toxicology and pharmacology are also prerequisites. A follow-up pattern of sequential and progressively more demanding assays through which IMT agents could be screened for therapeutic potential is suggested. The example of Imuthiol, tested accordingly, demonstrates the usefulness of the proposed procedure.

Adjuvants, Immunologic↗
PubMed1986

Clinical characterization of imuthiol.

Imuthiol is a nontoxic agent recruting and regulating T cells. Phase III studies in chronic bronchitis and bronchiectasis showed that immune functions were restored to normal, or near normal values. Cure was obtained in rheumatoid arthritis, tuberculosis and chronic infections in the elderly. Imuthiol is an effective agent for the treatment of syndromes and disease states where the underlying defect is a T-cell deficiency or dysfunction.

Acquired Immunodeficiency Syndrome↗