ArticleThe Journal of experimental medicine1996
Suppression of proinflammatory cytokines in monocytes by a tetravalent guanylhydrazone.
Article in The Journal of experimental medicine, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- CNS-Spleen Axis - a Close Interplay in Mediating Inflammatory Responses in Burn Patients and a Key to Novel Burn Therapeutics.Frontiers in immunology · 2021Pooled it
- Dual red and near-infrared light-emitting diode irradiation ameliorates LPS-induced otitis media in a rat model.Frontiers in bioengineering and biotechnology · 2023Article
- Neuro-immune interactions in inflammation and host defense: Implications for transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Review
- The multi-target effects of CNI-1493: convergence of anti-amylodogenic and anti-inflammatory properties in animal models of Alzheimer's disease.Molecular medicine (Cambridge, Mass.) · 2016Article
- Experimental Anti-Inflammatory Drug Semapimod Inhibits TLR Signaling by Targeting the TLR Chaperone gp96.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation.PloS one · 2015Article
- Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia.PloS one · 2014Article
- Neural reflexes in inflammation and immunity.The Journal of experimental medicine · 2012Review
- Microencapsulated drug delivery: a new approach to pro-inflammatory cytokine inhibition.Journal of microencapsulation · 2012Review
- Local and systemic chemokine patterns in a human musculoskeletal trauma model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2009Article
- CNI-1493 inhibits Abeta production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease.The Journal of experimental medicine · 2008Article
- The guanylhydrazone CNI-1493: an inhibitor with dual activity against malaria-inhibition of host cell pro-inflammatory cytokine release and parasitic deoxyhypusine synthase.Parasitology research · 2008Article
- Pathophysiology of pulmonary complications of acute pancreatitis.World journal of gastroenterology · 2006Review
- A novel inhibitor of inflammatory cytokine production (CNI-1493) reduces rodent post-hemorrhagic vasospasm.Neurocritical care · 2006Article
- Tumor necrosis factor as a pharmacological target.Molecular biotechnology · 2005Review
- Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy.The American journal of pathology · 2005Article
- Identification of cellular deoxyhypusine synthase as a novel target for antiretroviral therapy.The Journal of clinical investigation · 2005Article
- Reversing established sepsis with antagonists of endogenous high-mobility group box 1.Proceedings of the National Academy of Sciences of the United States of America · 2004Article
- [Role of the innate immune response in sepsis].Der Anaesthesist · 2004Review
- Prospects for the development of small molecular weight compounds to replace anti-tumour necrosis factor biological agents.Annals of the rheumatic diseases · 2003Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
An overproduction of proinflammatory cytokines by activated macrophages/monocytes mediates the injurious sequelae of inflammation, septic shock, tissue injury, and cachexia. We recently synthesized a tetravalent guanylhydrazone compound (CNI-1493) that inhibits cytokine-inducible arginine transport and nitric oxide (NO) production in macrophages, and protects mice against lethal endotoxemia and carrageenan-induced inflammation. During these investigations we noticed that CNI-1493 effectively prevented lipopolysaccharide (LPS)-induced NO production, even when added in concentrations 10-fold less than required to competitively inhibit L-arginine uptake, suggesting that the suppressive effects of this guanylhydrazone compound might extend to other LPS-induced responses. Here, we report that CNI-1493 suppressed the LPS-stimulated production of proinflammatory cytokines (tumor necrosis factor [TNF], interleukins 1beta and 6, macrophage inflammatory proteins 1alpha and 1beta) from human peripheral blood mononuclear cells. Cytokine suppression was specific, in that CNI-1493 did not inhibit either the constitutive synthesis of transforming growth factor beta or the upregulation of major histocompatibility complex class II by interferon gamma (IFN-gamma). In contrast to the macrophage suppressive actions of dexamethasone, which are overridden in the presence of IFN-gamma, CNI-1493 retained its suppressive effects even in the presence of IFN-gamma. The mechanism of cytokine-suppressive action by CNI-1493 was independent of extracellular L-arginine content and NO production and is not restricted to induction by LPS. As a selective inhibitor of macrophage activation that prevents TNF production, this tetravalent guanylhydrazone could be useful in the development of cytokine-suppressive agents for the treatment of diseases mediated by overproduction of cytokines.
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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.