Levamisole is an anthelmintic agent with immunomodulatory effects[1]. Treatment of human dendritic cells with 1 μM levamisole significantly promoted the secretion of IL-12 p40 and IL-10 secretion compared to the control group. Levamisole at 1 μM also further enhanced lipopolysaccharide (10 ng/mL)-induced production of IL-12 p40 and IL-10 in human dendritic cells. Levamisole-treated dendritic enhanced T cell activation towards type 1 cytokine balance. The NF-κB and JNK pathways were involved in levamisole-induced secretion of IL-12 p40 in dendritic cells[2]. In mice infected with 1,000 infective T canis larvae, subcutaneous administration of levamisole hydrochloride at a dose of 12 mg/kg/day from days 15 to 28 of infection decreased the infection in all organs[3].
作用机制
Levamisole exerts its immunomodulatory effects through cholinergic activity on T lymphocytes, resulting in an increase in the level of cyclic guanosine monophosphate in lymphocytes[1].
Levamisole/左旋咪唑 细胞实验
Cell Line
Concentration
Treated Time
Description
References
AS MSCs
100 μM
Inhibition of accelerated mineralization in AS MSCs
J Clin Invest. 2019 Dec 2;129(12):5357-5373
CD4+CD25-T cells
8 mg/ml, 40 mg/ml, 200 mg/ml
72 hours
suppressed T cell proliferation
Front Immunol. 2022 Jul 14;13:907808
DC2.4 cells
8 mg/ml, 40 mg/ml, 200 mg/ml
48 hours
inhibited TLR7 agonist-induced proinflammatory cytokine production
Front Immunol. 2022 Jul 14;13:907808
BMNCs (bone marrow nucleated cells)
40 mg/ml
48 hours
downregulated genes related to APCs and T cells
Front Immunol. 2022 Jul 14;13:907808
Regulatory T cells (Tregs)
8 mg/ml, 40 mg/ml, 200 mg/ml
72 hours
increased the proportion of Tregs
Front Immunol. 2022 Jul 14;13:907808
vascular smooth muscle cells (VSMCs)
200 μmol/L
The combination of TNAP inhibitor levamisole and eNTPD inhibitor ARL67156 increased extracellular pyrophosphate synthesis in LmnaG609G/ +VSMCs 2-fold, reduced pyrophosphate hydrolysis by 91%, and decreased calcium accumulation by 92%.
Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23698-23704
Human microvascular endothelial cells (HMVECs)
100 μg
24 hours
To assess the cytotoxic effects of Levamisole-induced NETs on endothelial cells. Results showed that Levamisole-induced NETs significantly enhanced endothelial cell apoptosis.
JCI Insight. 2017 Feb 9;2(3):e89780
Peripheral blood neutrophils from healthy human subjects
100 μM
3 hours
To evaluate the effect of Levamisole on neutrophil extracellular trap (NET) formation. Results showed that Levamisole significantly increased NET formation, which was dependent on the activation of NADPH oxidase and PAD4.
JCI Insight. 2017 Feb 9;2(3):e89780
Levamisole/左旋咪唑 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
CB6F1 mice
Immune-mediated bone marrow failure model
Oral
20 mg/kg
Once daily starting from day 0 until the mice died
Improved pancytopenia and prolonged survival, suppressed effector T cells and promoted regulatory T-cell expansion
Front Immunol. 2022 Jul 14;13:907808
Mice
LmnaG609G/ +mouse model
Intraperitoneal injection
0.2 mg/kg
Every 2 days, starting from 8 weeks of age until death or euthanasia
Combined treatment with ATP, levamisole, and ARL67156 significantly extended the lifespan of LmnaG609G/ +mice (from 38.2 to 42.8 weeks, 11.9%) and reduced aortic calcification (from 837.4 ±189.7 μg/g to 443.9±76.3 μg/g).
Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23698-23704
Mice
Aortic ring model
In vitro culture
100 μg
15 minutes
To evaluate the effect of Levamisole-induced NETs on vascular relaxation. Results showed that Levamisole-induced NETs significantly impaired endothelium-dependent vasorelaxation.
JCI Insight. 2017 Feb 9;2(3):e89780
Swiss albino male mice
Immunomodulatory activity evaluation model
Oral
50 mg/kg
14 days
Evaluate the immunomodulatory effects of Levamisole in mice, results showed Levamisole significantly increased thymus index (p<0.001).
Immunotargets Ther. 2024 Jan 23;13:15-27
BALB/c male mice
Cyclophosphamide-induced immunosuppressed mouse model
Oral gavage
10 mg/kg
Continuous for 28 days
To evaluate the immunomodulatory effects of levamisole hydrochloride on immunosuppressed mice. The results showed that levamisole hydrochloride significantly improved immune organ atrophy, restored intestinal morphology, and normalized cytokine levels, indicating enhanced immune function.
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