ArticleJCI insight2017
A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02257866 (Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis), which is not on this map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Neutrophil Extracellular Traps (NETs) and Vasculitis.International journal of medical sciences · 2021Pooled it
- Influence of the Cholinergic System on the Pathogenesis of Glioblastoma: Impact of the Neutrophil Granulocytes.International journal of molecular sciences · 2025Article
- Article
- Cocaine-Triggered PR3-ANCA Vasculitis Localized to a Post-Surgical Neck Field: A Case of Locus Minoris Resistentiae in Drug-Induced Autoimmunity.Diagnostics (Basel, Switzerland) · 2025Article
- First case of lupus induced by the Shingrix vaccine: a case report and literature review.Clinical rheumatology · 2025Review
- Advances in research of neutrophil extracellular trap formation in osteoarticular diseases.World journal of orthopedics · 2025Review
- Midline Destructive Lesions: Differentiating Granulomatosis With Polyangiitis From Cocaine-Induced Perforations.Cureus · 2025Article
- Contemporary insights into neuroimmune interactions across development and aging.Frontiers in neurology · 2025Review
- Cocaine- and Levamisole-Induced Vasculitis: Defining the Spectrum of Autoimmune Manifestations.Journal of clinical medicine · 2024Review
- Levamisole Impairs Vascular Function by Blocking α-Adrenergic Receptors and Reducing NO Bioavailability in Rabbit Renal Artery.Cardiovascular toxicology · 2024Article
- Down-regulation of SHP2 promotes neutrophil autophagy and inhibits neutrophil extracellular trap formation to alleviate asthma through the ERK5 pathway.Central-European journal of immunology · 2024Article
- NETosis Secondary to the Use of Levamisole-Adulterated Cocaine: A Likely Underlying Mechanism of Vasculopathy.Journal of toxicology · 2024Article
- Neutrophil extracellular trap formation in anti-neutrophil cytoplasmic antibody-associated and large-vessel vasculitis.Clinical immunology (Orlando, Fla.) · 2023Article
- Constitutively active Lyn kinase causes a cutaneous small vessel vasculitis and liver fibrosis syndrome.Nature communications · 2023Article
- Levamisole-induced and COVID-19-induced retiform purpura: two overlapping, emerging clinical syndromes.Archives of dermatological research · 2023Review
- Club cell CREB regulates the goblet cell transcriptional network and pro-mucin effects of IL-1B.Frontiers in physiology · 2023Article
- Cocaine-induced granulomatosis with polyangiitis-an under-recognized condition.Rheumatology advances in practice · 2023Article
- Modulation of the Itaconate Pathway Attenuates Murine Lupus.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19.JCI insight · 2022Article
- Cocaine/Levamisole-Induced, Skin-Limited ANCA-Associated Vasculitis with Pyoderma Gangrenosum-like Presentation.Dermatopathology (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Levamisole, an anthelmintic drug with cholinergic properties, has been implicated in cases of drug-induced vasculitis when added to cocaine for profit purposes. Neutrophil extracellular trap (NET) formation is a cell death mechanism characterized by extrusion of chromatin decorated with granule proteins. Aberrant NET formation and degradation have been implicated in idiopathic autoimmune diseases that share features with levamisole-induced autoimmunity as well as in drug-induced autoimmunity. This study's objective was to determine how levamisole modulates neutrophil biology and its putative effects on the vasculature. Murine and human neutrophils exposed to levamisole demonstrated enhanced NET formation through engagement of muscarinic subtype 3 receptor. Levamisole-induced NETosis required activation of Akt and the RAF/MEK/ERK pathway, ROS induction through the nicotinamide adenine dinucleotide phosphate oxidase, and peptidylarginine deiminase activation. Sera from two cohorts of patients actively using levamisole-adulterated cocaine displayed autoantibodies against NET components. Cutaneous biopsy material obtained from individuals exposed to levamisole suggests that neutrophils produce NETs in areas of vasculitic inflammation and thrombosis. NETs generated by levamisole were toxic to endothelial cells and impaired endothelium-dependent vasorelaxation. Stimulation of muscarinic receptors on neutrophils by cholinergic agonists may contribute to the pathophysiology observed in drug-induced autoimmunity through the induction of inflammatory responses and neutrophil-induced vascular damage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.