ArticleMolecular medicine (Cambridge, Mass.)
The selective alpha7 agonist GTS-21 attenuates cytokine production in human whole blood and human monocytes activated by ligands for TLR2, TLR3, TLR4, TLR9, and RAGE.
Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
108 citing papers in PubMed, 193 citations in OpenAlex.
- Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2016Trial
- Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Neuroimmune interactions in inflammatory bowel disease: Role of intestinal macrophages and the cholinergic pathway.World journal of gastroenterology · 2025Review
- The molecular components of the anti-inflammatory cholinergic pathway are extrasplenic.PloS one · 2025Article
- Choline in immunity: a key regulator of immune cell activation and function.Frontiers in immunology · 2025Review
- Effect of acetylcholinesterase inhibition on immune cells in the murine intestinal mucosa.Heliyon · 2024Article
- Basal forebrain cholinergic systems as circuits through which traumatic stress disrupts emotional memory regulation.Neuroscience and biobehavioral reviews · 2024Review
- Cholinergic signaling via the α7 nicotinic acetylcholine receptor regulates the migration of monocyte-derived macrophages during acute inflammation.Journal of neuroinflammation · 2024Article
- Activating α7nAChR suppresses systemic inflammation by mitigating neuroinflammation of the medullary visceral zone in sepsis in a rat model.Translational neuroscience · 2024Article
- Pharmacological and Electroceutical Targeting of the Cholinergic Anti-Inflammatory Pathway in Autoimmune Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Neuroimmune nexus in the pathophysiology and therapy of inflammatory disorders: Role of α7 nicotinic acetylcholine receptors.Pharmacological research · 2023Review
- Schizophrenia Etiological Factors and Their Correlation with the Imbalance of the Immune System: An Update.Galen medical journal · 2023Review
- Neurotoxins Acting at Synaptic Sites: A Brief Review on Mechanisms and Clinical Applications.Toxins · 2022Review
- Effect of Vagus Nerve Stimulation on Blood Inflammatory Markers in Children with Drug-Resistant Epilepsy: A Pilot Study.Children (Basel, Switzerland) · 2022Article
- Anti-inflammatory activity of nicotine isolated from Brassica oleracea in rheumatoid arthritis.Bioscience reports · 2022Article
- Anti-Inflammatory and Neuroprotective Mechanisms of GTS-21, an α7 Nicotinic Acetylcholine Receptor Agonist, in Neuroinflammation and Parkinson's Disease Mouse Models.International journal of molecular sciences · 2022Article
- Selective Agonists and Antagonists of α9 Versus α7 Nicotinic Acetylcholine Receptors.ACS chemical neuroscience · 2022Article
- Neuroimmune Regulation in Sepsis-Associated Encephalopathy: The Interaction Between the Brain and Peripheral Immunity.Frontiers in neurology · 2022Review
- Article
- Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3.Molecules (Basel, Switzerland) · 2021Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The cholinergic antiinflammatory pathway modulates inflammatory cytokine production through a mechanism dependent on the vagus nerve and the alpha7 subunit of the nicotinic acetylcholine receptor. GTS-21 [3-(2,4-dimethoxybenzylidene) anabaseine], a selective alpha7 agonist, inhibits inflammatory cytokine production in murine and human macrophages and in several models of inflammatory disease in vivo, but to date its antiinflammatory efficacy in human monocytes has not been characterized. We report here our findings that GTS-21 attenuates tumor necrosis factor (TNF) and interleukin 1beta levels in human whole blood activated by exposure to endotoxin. GTS-21 inhibited TNF production in endotoxin-stimulated primary human monocytes in vitro at the transcriptional level. The suppressive effect of GTS-21 was more potent than nicotine in whole blood and monocytes. Furthermore, GTS-21 attenuated TNF production in monocytes stimulated with peptidoglycan, polyinosinic-polycytidylic acid, CpG, HMGB1 (high-mobility group box 1 protein), and advanced glycation end product-modified albumin. GTS-21 decreased TNF levels in endotoxin-stimulated whole blood obtained from patients with severe sepsis. These findings establish the immunoregulatory effect of GTS-21 on human monocytes, and indicate the potential benefits of further exploration of GTS-21's therapeutic uses in human inflammatory disease.
Indexed as
Identifiers
What OpenQuestion holds
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.