The comparative effects of isoprinosine, levamisole, muramyl dipeptide and SM1213 on lymphocyte and macrophage proliferation and activation in vitro

Hadden, John W.; Englard, Arthur; Sadlik, John R.; Hadden, Elba M.

doi:10.1016/0192-0561(79)90026-2

Cited by 87 publications

(19 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(MDP), Mr 492] is the minimal structural unit with immune potentiating activity that can replace mycobacteria in Freund's complete adjuvant (8)(9)(10). MDP is known to influence many macrophage functions such as the production of prostaglandins and collagenase (11), motility (12), enhanced 02 generating capacity (13), proliferation in response to lymphokines (14), cytolytic activity (15), and production of lymphocyte-activating factors (16). Moreover, MDP encapsulated within liposomes-concentric phospholipid vesicles separated by aqueous compartments-can render rat alveolar macrophages (AM) tumoricidal in vitro (17).…”

mentioning

confidence: 99%

Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide.

Fidler¹,

Sone²,

Fogler³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

291

130

View full text Add to dashboard Cite

The multiple systemic administration of multilamellar liposomes composed of phosphatidylserine and phosphatidylcholine (molar ratio 3:7) that contained water-soluble muramyl dipeptide (MDP) activated alveolar macrophages to become tumoricidal and eradicated established spontaneous pulmonary and lymph node metastases. Spontaneously metastasizing melanoma cells were injected into the footpads of mice. After 4-5 weeks, the tumors were resected by a midfemoral amputation; 3 days later, twice-weekly injections of liposomes were initiated and continued for 4 weeks. In some experiments the mice were killed 2 weeks after the final treatment. Seventy-four Percent of animals injected with liposomes containing MDP were free of visible metastases. In a separate life-span experiment, 60% of mice treated with liposome-encapsulated MDP were tumor-free 120 days after the last liposome treatment or 110 days after all control mice treated with free MDP or control liposome preparations had died of disseminated cancer. These data suggest that the systemic administration of liposomes containing MDP, or similar compounds that produce macrophage activation, may provide an additional useful approach to the therapeutic regimens currently used to eradicate cancer metastases.Metastasis of malignant neoplasms is responsible for most therapeutic failures in clinical oncology (1-3). Recent studies suggested that metastases can result from the proliferation of a minor subpopulation of cells within the primary tumor and that tumors can be heterogeneous with regard to many phenotypic characteristics such as drug sensititivity and metastatic potential (1-3). Such biological diversity among metastases implies that successful therapy of disseminated disease must include a regimen that acts by a mechanism independent of this heterogeneity.One biological agent that appears to function against tumor cells without regard to their phenotypic diversity is the activated macrophage. At least in vitro, macrophages can distinguish tumorigenic from nontumorigenic cells by a mechanism that is independent of such phenotypic characteristics as drug sensitivity, metastatic potential, and antigenicity (4). Moreover, to date, attempts to select in vitro tumor cells resistant to macrophage-mediated cytotoxicity have been unsuccessful (5).The increasing evidence that macrophages are important in host defense against neoplasia has stimulated interest in agents that can enhance macrophage-mediated destruction of tumor cells. Normal macrophages can be activated to become tumoricidal by various agents such as lymphokines and by whole microorganisms or their products such as endotoxins (6). However, the use of whole viable microorganisms or their products to activate macrophages in vivo has been hampered by a number of undesirable side effects (7).The search for synthetic compounds that are relatively nontoxic yet possess immune potentiating activities has resulted in the demonstration that N-acetylmuramyl-L-alanyl-D-isoglutamine [muramyl dipeptide. (MDP), Mr 49...

show abstract

mentioning

confidence: 99%

Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide.

Fidler¹,

Sone²,

Fogler³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

291

130

View full text Add to dashboard Cite

show abstract

“…DISCUSSION When PEC were infected and incubated with SM-1213, the most significant drug-induced reductions in hyphal growth and candidal viability occurred at the 1 ng/ml drug level (Tables 1 and 2). Higher or lower concentrations of drug were less effective, reflecting the bell-shaped dose-response curve frequently observed for immunomodulatory drugs (6,7). Others (D. L. Cahall and R. Conklin, Program Abstr.…”

Section: Methodsmentioning

confidence: 99%

“…These compounds have been termed "pro-host" (7) because, rather than being directly microbicidal, they enhance the ,antimicrobial activities of host defense cells. Included in such leukocyte-modulating substances are semisynthetic or wholly synthetic agents such as muramyl dipeptide (3,7), inosiplex (7), and levamisole (5,7). Another such agent is SM-1Z13, a syn heticJ substituted monosaccharide that is reported to potentiate macrophage bactericidal activity (7).…”

mentioning

confidence: 99%

“…Included in such leukocyte-modulating substances are semisynthetic or wholly synthetic agents such as muramyl dipeptide (3,7), inosiplex (7), and levamisole (5,7). Another such agent is SM-1Z13, a syn heticJ substituted monosaccharide that is reported to potentiate macrophage bactericidal activity (7). The enhancing effects of SM-1213 on the fungistatic or fungicidal capacities of guinea pig peritoneal exudate cells (PEC) against both the yeast and hyphal forms of Candida albicans, a clinically important dimorphic fungus (8), are described in this report.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Enhanced killing of Candida albicans by cultured peritoneal exudate cells treated with SM-1213, a synthetic immunomodulator

Morrison¹,

Gordon²,

Hashimoto³

1984

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The effect of SM-1213 [1,2-O-isopropylidene-3-O-3'-(N', N'-dimethylamino-n-propyl)-D-glucofuranose] on the candidastatic and candidacidal capacity of guinea pig peritoneal exudate cells was investigated. Phagocytes treated with SM-1213 demonstrated an enhanced ability to inhibit intracellular hyphal formation and elongation of Candida albicans cells as well as to reduce the percentage of viable cells remaining after phagocytosis. Significant drug-induced anticandidal effects were also observed when peritoneal exudate cells were preincubated with SM-1213 and washed before infection with C. albicans. SM-1213 had no direct anticandidal effect against the yeast or hyphal form of the fungus, suggesting that the observed candidastatic and candidacidal effect of this drug was due to the enhancement of antimicrobial functions of phagocytes.

show abstract

“…However, direct antiviral agents and actions that alter host immunity are reported to have varying effects on the course of the disease [3, 4, 12, 14, 15, 18, 25, 26, 281. I t has been proposed that inosiplex may have an influence on viral diseases because of its direct antiviral and immunomodulatory properties [2,4,7,[19][20][21][22]27, 301. Huttenlocher and Mattson [12] and Streletz and Cracco [28] reported that inosiplex was beneficial in reducing the morbidity and mortality associated with SSPE.…”

mentioning

confidence: 99%

Long‐term follow‐up of patients with subacute sclerosing panencephalitis treated with inosiplex

Dyken

Swift

DuRant

1982

Annals of Neurology

106

View full text Add to dashboard Cite

During the past five years, 15 patients with subacute sclerosing panencephalitis (SSPE) were treated with inosiplex. Using a disability index specifically designed for the disease, this study monitored the course of SSPE in each patient before and during inosiplex therapy. Posttreatment follow-up ranged from 2 to 144 months. Inosiplex had an apparently beneficial effect on morbidity and mortality in 10 of the 15 patients tested. Eight improved immediately after treatment, 2 had a delayed improvement, and 1 patient stabilized. Four patients followed a typical course for SSPE and died a mean 9 months after onset. Treatment was not associated with adverse reactions. Due to its low risk-benefit ratio, inosiplex is recommended for continuous use in SSPE even after extended remissions.

show abstract

The comparative effects of isoprinosine, levamisole, muramyl dipeptide and SM1213 on lymphocyte and macrophage proliferation and activation in vitro

Cited by 87 publications

References 15 publications

Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide.

Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide.

Enhanced killing of Candida albicans by cultured peritoneal exudate cells treated with SM-1213, a synthetic immunomodulator

Long‐term follow‐up of patients with subacute sclerosing panencephalitis treated with inosiplex

Contact Info

Product

Resources

About