[Immunodepression by levamisol].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G Renoux.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
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.
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.
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.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Levamisole and sodium diethyldithiocarbamate can induce in vivo thymocyte differentiation from precursor spleen cells of nu/nu mice and evoke indirect plaque-forming cells in nude mice immunized with sheep red cells. These sulphur drugs induce in thymusless mice the production of a serum factor which transfer in vivo immune enhancement and in vitro thymocyte differentiation. In vivo treatment with sulphur derivative can substitute for an alleged thymice hormone.
Phenol-water extracts from smooth B. melitensis or B. abortus induce specific proliferation of lymphocytes from Brucella-sensitized men or animals. These extracts have no effect on lymphocytes of uninfected subjects. Above findings imply that an antigen will not trigger the so-called primary response when administered to a immune virgin animal.
Explore the source record for details and available documents.
A single dose of DTC was administered, in a dose-range from 0.6 mg/kg to 25 mg/kg, to mice immunized with 10(8) sheep red cells (SRC). All doses strongly enhanced plaque-forming spleen cell (PFC) responses, when given either 18 h before, simultaneously to, 6 h or 24 h after SRC immunization. However, the higher levels of immunostimulation were attained by DTC doses above 5 mg/kg. DTC-induced immunopotentiation was not accompanied by untoward effects, such as acute toxicity, splenomegalia or modifcations in counts of viable spleen lymphocytes.
The effects of levamisole were studied by evaluating T-cell responsiveness to a low dose of PHA on 31 advanced cancer volunteers. Treatment consisted in a 3-time a week oral administration of 150 mg of levamisole, actual time of observation is comprized between 10 and 31 months: 14 out of 31 treated metastatic cases of various solid tumours are still alive. In a group of 25 untreated patients, mean survival times were 65 days for men and 48 days for women. An increase of the responsiveness to a low dose of PHA was associated with survival, while death occurred when T-cells were unable to respond to the stimulatory activity of levamisole. These preliminary data confirm the paramount importance of cellular immunity in controlling neoplasias. They suggest a possibility to augment the life-span of cancer patients if an impaired cellular immunity machinery could be restored by the direct and indirect (hormonal) actions of levamisole, evidencing these mechanisms were still potentially functionning. They suggest also a monitoring of anti-tumoral immunity by evaluating the magnitude of T-cell response following levamisole administration.
Explore the source record for details and available documents.