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At least 19 recordsLinked to original sources
PubMed1976

In vitro stimulation of neutrophil motility by levamisole: maintenance of cgmp levels in chemotactically stimulated levamisole-treated neutrophils.

Levamisole at concentrations of 10(-3) M or 10(-4) M consistently increased neutrophil random motility and chemokinesis (stimulated random migration). Similar concentrations also increased directional movement of polymorphonuclear leukocytes to both endotoxin-activated serum and hydrolyzed casein. This effect on chemotaxis was due to a true stimulation and was not due solely to increased random movement. The effect of levamisole on the neutrophils could be removed by washing, but persisted if the cells were initially treated with levamisole and serum or endotoxin-activated serum. After neutrophil stimulation with chemotactic factor an initial rise in intracellular cyclic AMP levels was detected which was not influenced by prior levamisole treatment. Intracellular cyclic GMP levels after an initial slight depression, returned to resting levels and gradually diminished over a 60-minute period. Levamisole-treated cells consistently showed higher cyclic GMP levels and it is postulated that by maintaining intracellular cyclic GMP levels, microtubular assembly and cell motility might be enhanced.

Caseins↗
PubMed1978

Levamisole in rheumatoid arthritis. A randomised double-blind study comparing two dosage regimens of levamisole with placebo. Multicentre study group.

The therapeutic effect of levamisole in patients with rheumatoid arthritis was evaluated in a sixteen-centre double-blind controlled study which compared continuous and intermittent levamisole treatment with placebo for six months. 363 patients with classic or definite rheumatoid arthritis and active disease were evaluated. Continuous and intermittent levamisole treatments were equally effective in controlling disease activity. 20% of patients had important drug-related adverse reactions. The results demonstrated that levamisole is an active drug in patients with rheumatoid arthritis.

Administration, Oral↗
PubMed1978

Effects of levamisole on normal and malignant murine lymphocytes.

Levamisole enhanced transformation of murine lymphocytes stimulated either by mitogens or allogeneic lymphocytes. In a similar dose-dependent pattern it stimulated in vitro growth of L1210, P1798, and 6C3HED but not YAC lymphoma cells. Stimulation of growth of lymphoma cells was greater by peritoneal cells harvested from normal mice 4 days after levamisole injection than by peritoneal cells from untreated mice. This effect correlated with the shortened survival time of BALB/c mice treated with levamisole prior to P1798 implantation compared to that of a control group not pretreated. Administration of levamisole with iodoacetamide-modified tumor cells in immunoprophylaxis studies had no effect on the rejection of a tumor implant or on development of tumor-specific antibody. Levamisole was added to regimens involving asparaginase therapy of 6C3HED-bearing C3H mice and chemoimmunotherapy of BALB/c mice bearing P1798 with methotrexate and iodoacetamide-modified P1798 cells. In neither case were there increased numbers of survivors, and mean survival time was generally decreased for the levamisole-treated groups. The stimulated tumor growth may have been mediated by a direct effect of levamisole on the lymphoma cells, through an effect on other cell types, or by both effects; these effects apparently outweighed potentially beneficial effects of levamisole on the immune system.

Animals↗
PubMed1979

Levamisole in the treatment of Hodgkin's disease.

In vitro and in vivo action of levamisole has been studied in patients with Hodgkin's disease. In vitro levamisole significantly increased the active T cell count of 35 untreated active patients, of those being in complete remission after treatment and of 19 healthy controls; it significantly raised the total T cell count of patients. However, levamisole could not further improve the considerably increased active and total spontaneous rosette formation resulting from in vivo levamisole treatment. Twenty patients with Hodgkin's disease, being in complete remission, were given levamisole for 3 or 6 months, according to 2 different schedules. Levamisole (150 mg) given on 3 consecutive days of every second week for 3 months considerably increased the number of positive skin tests (from 8/60 to 29/60), the numbers of active and total T cells with unchanged absolute lymphocyte count, and decreased the quantity of circulating immune complex. Continuation of treatment for another 3 months resulted in slight, but consistent, decline in all the above parameters; the ratio of active T cells significantly decreased. This decline was even more pronounced if a raised larger dosage of levamisole was administered for 6 months. In the course of the treatment no side-effect or complication was observed. Levamisole is able to improve the weak cellular immune reactivity of patients with Hodgkin's disease, it can, however, result in undesired suppression in the case of too long treatment with high dose.

Adult↗
PubMed1979

Effect of levamisole on the mitosis of murine thymocytes in culture.

The effect of levamisole on murine thymocytes stimulated by concanavalin A in culture was measured as the change in number of cells in the DNA synthetic phase (S-phase) and in number of cells undergoing mitosis (M-phase). Addition of levamisole to Con A-stimulated lymphocytes led to an approximately tenfold increase in the frequency of mitosis and a fivefold increase in the frequency of cells heavily labeled with thymidine. Thus, levamisole leads to an increased number of cells undergoing proliferation. Determination of cell viability excluded the possibility that the effect of levamisole was simply due to enhanced numbers of viable cells in culture. Examining the effect of levamisole on the proliferating cells alone, it was found that they had a shorter cell cycle time. It was therefore concluded that levamisole affects thymocyte proliferation in vitro in two ways: enhancement of the number of proliferating cells and shortening the cell cycle time of proliferating cells. A similar effect in vivo might be important in the mechanism of action of levamisole as an immunotherapeutic agent.

Animals↗
PubMed1977

Levamisole-induced immunostimulation in spondylarthropathies.

The term "seronegative spondylarthritis" (S.S.A.) has been assigned to rheumatic disorders with closely related clinical features, defined by seronegativity and HLA-B27 phenotype. Its pathogenesis may be linked with a genetically controlled defective immune response. Therefore, 37 men with S.S.A. were treated with levamisole (150 mg/day, 3 days/wk) to stimulate the immune reactions. In a randomised controlled crossover study these patients also received a placebo; each period ran for 12 wk. Symptomatic therapy was continued through the entire 6 mo. Serious side-effects led to withdrawal of the active drug in 9 patients. Clinical response was measured in terms of a cumulative joint index, spondylometry, morning stiffness, and a pain scale. Treatment with levamisole resulted in a significant improvement in these parameters. Radiological evidence of sacroiliitis was present in 48.6% before and after levamisole, and joint scanning with 99Tc-pyrophosphate also revealed no progress in the disease. After levamisole treatment, IgM levels fell significantly (P less than 0-014). Likewise, the previously high percentage of antibodies with weak cytotoxic activity against lymphocytes was reduced after levamisole (P less than 0-049), and an increased rate of leucocyte-migration inhibition (L.M.I) was found in the levamisole-treated group. Thus, the immunostimulating properties of levamisole may interfere with defective immunoregulation in S.S.A. and, by improving the clinical conditions, lead to a change in the course of this disease.

Adult↗
PubMed1978

A double-blind, controlled trial of levamisole in the treatment of recurrent herpes labialis.

A double-blind, controlled trial of levamisole in the prevention and treatment of recurrent cold sores was performed. Forty-eight subjects received levamisole in a dosage of 2.5 mg/kg on two consecutive days each week for six months. The 51 control subjects were given a placebo identical to the drug in appearance. Both groups were given the same instructions. Nineteen subjects receiving levamisole and eight receiving placebo withdrew during the six months of the study. There were no significant differences between the levamisole-treated and control groups in the duration or severity of the lesions during the trial period or in the subjective assessment of drug efficacy by the participants at the end of the trial. Before treatment the frequency of lesions in the levamisole group was higher than in the control group. Only when this factor was taken into account by analysis of covariance did the decreased frequency of lesions during therapy appear significantly lower in the group receiving levamisole than in the placebo group. The difference remained clinically unimpressive. This study does not support earlier suggestions that levamisole, in these doses, is useful in the treatment of recrudescent circumoral herpesvirus infections.

Clinical Trials as Topic↗
PubMed1978

Enhancement of neutrophil chemotaxis and alteration of levels of cellular cyclic nucleotides by levamisole.

Levamisole, an antihelminthic agent reported to enhance nonspecifically various parameters of the immune response, was examined for its effect on chemotaxis of human neutrophils and on levels of cellular cyclic nucleotides. This agent was found, in most instances, to enhance chemotactic responses of neutrophils to a bacterial chemotactic factor derived from Escherichia coli. At similar concentrations, levamisole produced increases in levels of guanosine 3':5'-cyclic phosphate in neutrophils. In contrast, a decrease in concentrations of adenosine 3':5'-cyclic phosphate was observed when neutrophils were incubated with levamisole. Neutrophil chemotaxis, with and without the addition of levamisole, was assessed in 10 patients with recurrent infections. The illnesses of these patients included Job's syndrome, Wiskott-Aldrich syndrome, eczema with an increased level of IgE and recurrent abscesses, chronic mucocutaneous candidiasis, and diabetes mellitus. Levamisole significantly enhanced chemotaxis of polymorphonuclear leukocytes from these patients. Levamisole appears to have a profound effect on chemotactic responses of neutrophils which probably results from alterations in cellular cyclic nucleotide levels. Levamisole may prove to be useful therapeutically in certain patients with defective neutrophil chemotaxis.

Chemotaxis, Leukocyte↗
PubMed1979

Induction of suppressor activity on B-cell differentiation in human T-cell subset without fc(IgG) receptors by levamisole administration.

A single oral dose of 150 mg levamisole was administered to five healthy adults. Circulating Fc(IgG) receptor-bearing T cells (T gamma cells) increased for 5 days after levamisole intake, but total E rosette-forming cells showed no significant alterations. The generation of immunoglobulin-producing cells in the peripheral blood lymphocytes (PBL), which was induced in the in vitro pokeweed mitogen (PWM)-stimulated cultures, was significantly suppressed for 5 days after levamisole administration. Suppressor T-cell activity on B-cell differentiation, which was induced by levamisole intake, was evaluated by co-culturing with allogeneic untreated adult PBL in the PWM system in six other volunteers. A seemingly dose-dependent suppression on B-cell differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells which were isolated before or on day 14 of the experiment. When T cells were fractionated into two subsets with regard to the presence or absence of Fc(IgG) receptors, suppressor T-cell activity appeared to be generated by levamisole largely in T cells lacking Fc(IgG) receptors, but not in T gamma cells.

Adult↗
PubMed1978

Levamisole in ascariasis. A multicenter controlled evaluation.

An analysis is presented of 10 clinical studies from various countries where levamisole 50--150 mg was compared to pyrantel, piperazine, and placebo in a total of 1,734 patients, mostly children (levamisole: 830, controls: 904), suffering from ascariasis either as a single infection or usually mixed with other nematode infections. Degree of infection and efficacy of treatment were determined by quantitative coproparasitological methods. Levamisole produced higher cure rates (91%) and egg reduction rates (98%) than pyrantel, piperazine, or placebo. The efficacy of levamisole was unrelated to the patients' sex and age, the severity of infection, the presence of another worm infection, the type of associated worm infections, or the egg-counting technique. The overall incidence of reported adverse reactions was lower after levamisole than after piperazine, pyrantel or placebo; abdominal pain and headache, the most frequent complaints after levamisole, were related to the initial severity of ascariasis. Follow-up examinations 6 months after treatment suggested that levamisole might delay reinfection.

Adolescent↗
PubMed1979

Immunotherapy of gastrointestinal cancer patients with levamisole.

Levamisole was administered to 177 patients with gastrointestinal cancer (88 curative resection, 58 noncurative resection and 31 without resection). It was administered at a daily dose of 150 mg for three consecutive days every other week. The administration was started, as a rule, 3 days before operation. This medication was repeated as frequently as possible at least for one month. The cellular immunity and 18-month survival rate of treated and control groups were compared. Levamisole effectively improved peripheral lymphocyte blastformation against phytohemagglutinin and increased the numbers of peripheral blood lymphocytes. Levamisole caused extremely high blastformation rates, in general, enhanced PPD reactions in non-curative resection cases 7 months after operation and showed no influence upon the number of peripheral blood lymphocyte. The effect of levamisole on the 6-month survival rate was most marked in patients without resection. Increased 12-month survival rate was marked in non-curative resection cases and, to a lesser extent, curative resection cases. Patients without resection had a slightly improved 12-month survival rate. Levamisole improved the 18-month survival rate in resectable cases; however, there were no significant differences in 18-month survival between levamisole and control groups of patients not undergoing resection. The results suggest that levamisole is effective in the patients whose tumor cells have been decreased by any method.

Esophageal Neoplasms↗
PubMed1979

[Levamisole as an immunostimulating factor].

Levamisole--(L)--1-2, 3, 5, 6--tetrahydro-6- phenylimidazo (2, 1-b)-- thiazol monohydrochloride, a simple chemical, first introduced as a broad spectrum antihelmintic , has been recently on the list of the nonspecific active immunostimulants together with BCG, Corynebacterium parvum, polyribonucleosides and transfer factor (TF). This, however, is oversimplification and may cause some confusion because levamisole, in contrast to the so-called immunostimulants, does not stimulate immunity above the normal level in man or prevent the primary growth of most experimental tumors in immunologically normal animals. Levamisole acts as an antianergic chemotherapeutic agent as it restores cell-mediated immunity in immunodepressed patients and prolongs the remission period. It even increases the number of long-term survivors when used as an adjunct to cytoreductive therapy in several animal cancer models. Levamisole is rapidly absorbed from the gastrointestinal tract and from injection site and is very well distributed in all tissues. Levamisole increases phagocytosis by polymorphonuclear cells or macrophages when added to these cells or given to donor animals and humans. The effect was pronounced on hypofunctional cells from patients and it was weak or absent on cells from normal donors. Chemotactic responsiveness of polymorphonuclear cells and monocytes from patients with defective leucocyte motility could be enhanced by levamisole added in vitro or given in vivo. The leucocyte migration inhibition in response to antigenic stimulation could be restored when levamisole was administered to anergic patients or added to their cells in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1979

Potentiation of L1210 murine leukemia vaccine in vivo by levamisole.

Intraperitoneal inoculation of either levamisole or 2 x 10(6) cells of concanavalin-A (Con-A)-bound L1210 leukemia vaccine produced no cured mice after subsequent ip inoculation of 10(3) live L1210 cells. Combined inocluation of levamisole and Con-A-bound vaccine produced about 20% cure incidence but no prolongation of life span of tumor-bearing mice after inoculation of live L1210 cells. Combined inoculation of levamisole and Con A-free vaccine did not induce detectable immune resistance in mice. These results suggest that levamisole enhanced host response to cell-bound Con-A associated with immunogenic potency of the vaccine. Levamisole given intravenously and orally was as effective as that inoculated intraperitoneally in enhancing the induction of resistance in mice by Con-A-bound vaccine. Dose of levamisole was very critical for this enhancement, being effective at 0.38 mg/kg but not either at 0.75 or 0.19 mg/kg. Furthermore, levamisole restored immune resistance induced by a larger inoculum of Con-A-bound vaccine cells (10(7)) and impaired by cyclophosphamide.

Adjuvants, Immunologic↗
PubMed1979

Combined chemoimmunotherapy for advanced breast cancer: a comparison of BCG and levamisole.

One hundred and fourteen evaluable patients with metastatic breast cancer were treated with a program consisting of 5-FU, Adriamycin, cyclophosphamide (FAC) and nonspecific immunotherapy with Levamisole. The results of this treatment program were compared to those observed with FAC and Bacillus Calmette Guerin (BCG) and FAC chemotherapy alone, both groups treated prior to the study reported in this paper. The overall response rates and complete response rates for all three treatment regimens were identical. The duration of remission, survival of all patients and survival of responders was similar for both chemoimmunotherapy regimens, being superior to the FAC chemotherapy alone group. Immunotherapy with Levamisole was well tolerated and side-effects were experienced by less than one-fourth of the patients. Overall, Levamisole was better tolerated than BCG and was easier to administer than the latter drug. These results suggest than nonspecific immunotherapy with Levamisole might prolong remission and survival of patients with metastatic breast cancer. Since the results achieved with BCG and Levamisole appear similar, the therapeutic ratio favors the use of Levamisole.

Antineoplastic Agents↗
PubMed1979

Actinomycin-D, levamisole chemoimmunotherapy of refractory malignant melanoma.

Sixty adult patients with disseminated melanoma refractory to DTIC or Dacarbazine were given chemoimmunotherapy with intermittent high single dose Actinomycin-D and Levamisole. Actinomycin-D was given at a dose of 1.5-2.0 mg/m2 intravenously every 3 to 4 weeks. Levamisole was given in a dose of 150 mg/day for two consecutive days each week (50 patients) and in a dose of 200 mg every other day (10 patients). Antitumor responses consisted of 2% complete remissions (CR), 2% partial remissions (PR), and 33% disease improvement less than PR or stabilization (S). Comparison of these patients who received Actinomycin-D + Levamisole with those on an immediately preceding study in a similar population where Actinomycin-D was given as a single agent revealed no difference in response rates. Patients who responded to Actinomycin-D + Levamisole (CR + PR + S) survived significantly longer (35 weeks) than nonresponders (12 weeks, p less than 0.01). Survival was not longer (p less than .05) in responding patients (CR + PR + S) receiving Actinomycin-D + Levamisole (35 weeks) compared to those responding to Actinomycin-D alone (18 weeks, p = 0.09). Hematologic toxicity was tolerable with median lowest granulocyte counts of 1.6 x 10(3)/microliter and platelet counts of 134,000/microliter. Other toxic effects were predominantly nausea, vomiting, and mucositis. In those patients who received alternate day Levamisole there was greater gastrointestinal upset as well as fever, rash and central nervous system toxicity which was unacceptable.

Adult↗
PubMed1977

Condition-dependent immunoregulatory control of contact sensitivity by levamisole.

The immunostimulatory activity of levamisole [1-(-),2,3,5,6-tetrahydro-6-phenylimidazo(2,1-beta)-thiazole] was investigated using oxazolone-induced contact sensitivity in C57Bl mice. Oxazolone sensitivity was induced by applying 0.1 ml of 3 or 5% oxazolone in ethanol to the shaved abdomen (day 0). Challenge with oxazolone followed on day 2 (45 h) or day 3, and was accomplished by painting a 1--5% solution of oxazolone in ethanol to the left hind paw. The response at 24 h was determined plethysmographically. Levamisole (50 mg/kg, p.o., days 0--3 or day 0 only) failed to stimulate consistently the oxazolone response in a 3-day (minimal) sensitization period regimen. Use of a subliminal (45 h) sensitization, by contrast, revealed a consistent immunostimulatory effect of levamisole (12.5--100 mg/kg, p.o., day 0 only). It is speculated that the observed difference in levamisole effectiveness is attributable to (1) the ability of levamisole to stimulate both effector and suppressor mechanisms, and (2) the apparent absence of significant suppressor influence at 2-day postsensitization, leaving only the effector mechanism to be stimulated by levamisole.

Animals↗