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Biomedical subjects

G Renoux

Publications and source records attributed to G Renoux.

At least 73 records · Page 4Linked to original sources

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↗

Thymus-like activities of sulphur derivatives on T-cell differentiation.

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.

Animals↗

[Sodium diethyldithiocarbamate is a stimulating agent of immunity].

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.

Animals↗

[Influence of the administration of levamisole on the reactivity of T-lymphocytes in advanced cancer patients].

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.

Administration, Oral↗

[Cachexia in mice induced by a fraction of Brucella melitensis. Modification by levamisole or by diethyldithiocarbamate of soda].

The PMF fraction of B. melitensis creates a wasting disease in newborn mice (J. infect. Dis., 1973, 127, p. 139). Administered to adult mice, PMF induces a 4 to 8 g loss of weight in 20 g mice and more markedly in males than in females. Treatment with Levamisole (LMS) suppresses this difference in response to PMF and restores normal weight in 24 days. Diethyldithiocarbamate (DDC), another immunostimulant sulfur derivate, abolishes the emaciating effect of PMF. Furthermore, DDC is an anabolizing agent which increases the weight of normal or PMF-treacted mice above the mean level of normal untreated control mice.

Animals↗

[Mitogenic activity of Brucella fractions on cultured lymphocytes].

LPS from smooth B. melitensis extracted by the phenol-water method has no mitogenic activity for lymphocytes of men or mice uninfected by brucellosis, in amounts that are not toxic in vitro for these cells. Mitogenic activities of other B. melitensis fractions are evidenced only in amounts 100-fold greater than an effective dose of LPS from E. coli. We interpret these findings as reflecting a virgin immune status against brucella antigens.

Animals↗

Potentiation of T-cell mediated immunity by levamisole.

Cell-mediated immunity is a requirement for recognition and elimination of cells and for prevention or treatment of a variety of diseases. Therefore, the development of a product potentially active in increasing immunity involves its testing in assays specific for cell-mediated immunity. The effectiveness of a single administration of levamisole was demonstrated in the rejection of isografts in a male to female C57BL/6 system, and on the enhancement of levels of the delayed type hypersensitivity (DTH) to sheep red cells (SRBC). Indeed, in five on nine tests, an injection of 25 mg/kg of levamisole to female recipients either on the day of grafting or 7 days after grafting resulted in a RT50% rejection time of 25 days, compared with 46 days in untreated controls. Levamisole administered at the time of immunization with various doses of SRBC elicited earlier, higher and more sustained DTH levels than in untreated controls. Such induction of T-cell activation was accompanied by a switch on anti-SRBC antibodies from IgM to IgG. These findings confirm and extend data evidencing the ability of levamisole to recruit and activate T cells for an increased or restored cell-mediated immunity.

Animals↗

[Biological properties and chemical composition of a soluble fraction of Brucella abortus. Monospecific A or M antigens].

ABS, the supernatant of smooth B. abortus phenol-protected suspensions, is a protein, lipid, sugar and ARN complex containing all amino acids found in phenol-water fractions from B. abortus and B. melitensis. ABS is non-toxic and immunizes mice against B. abortus challenge. Chromium chloride easily binds ABS to sheep erythrocytes (E ABS) for a specific and accurate passive hemagglutination test in brucellosis. E ABS are agglutinated by all antisera to fractions of B. abortus or B. melitensis, but not by the monospecific anti M serum. A study of the antigenic relationships between ABS and phenol-water fractions from smooth brucella strains leads to the isolation of sub-fractions fron the phenol precipitates of B. abortus or of B. melitensis that could contain only A or M antigens which react only with their respective monospecific A or M serum.

Amino Acids↗