ArticleJournal of inflammation (London, England)2019
LDK378 improves micro- and macro-circulation via alleviating STING-mediated inflammatory injury in a Sepsis rat model induced by Cecal ligation and puncture.
Article in Journal of inflammation (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Current status and challenges of immunotherapy in ALK rearranged NSCLC.Frontiers in oncology · 2022Pooled it
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- cGAS-STING targeting offers novel therapeutic regimen in sepsis-associated organ dysfunction.Cell biology and toxicology · 2025Review
- cGAS-STING targeting offers therapy choice in lung diseases.Biology direct · 2025Review
- cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases.Drug design, development and therapy · 2025Review
- The dysfunction of complement and coagulation in diseases: the implications for the therapeutic interventions.MedComm · 2024Review
- Review
- Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms.Journal of clinical medicine · 2023Review
- The STING1-MYD88 complex drives ACOD1/IRG1 expression and function in lethal innate immunity.iScience · 2022Article
- Oncology Drug Repurposing for Sepsis Treatment.Biomedicines · 2022Review
- STING1 in sepsis: Mechanisms, functions, and implications.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2022Review
- MicroRNA-381-3p signatures as a diagnostic marker in patients with sepsis and modulates sepsis-steered cardiac damage and inflammation by binding HMGB1.Bioengineered · 2021Article
- Signaling pathways and intervention therapies in sepsis.Signal transduction and targeted therapy · 2021Review
- The Innate Immune cGAS-STING-Pathway in Cardiovascular Diseases - A Mini Review.Frontiers in cardiovascular medicine · 2021Review
- Augmented Renal Clearance: What Have We Known and What Will We Do?Frontiers in pharmacology · 2021Review
- The hallmarks of COVID-19 disease.PLoS pathogens · 2020Review
- TMEM173 Drives Lethal Coagulation in Sepsis.Cell host & microbe · 2020Article
- Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSepsis is a systemic inflammatory response syndrome caused by severe infections. LDK378, a second-generation ALK inhibitor, exhibits a potential anti-inflammatory function against sepsis. Micro- and macro-circulatory dysfunctions are pivotal elements of the pathogenesis of severe sepsis and septic shock. We hypothesized that LDK378 can improve micro- and macro-circulation of septic rats, therefore improving the outcome of survival via blocking the ALK-STING pathway to attenuate inflammatory injuries.
methodsA septic rat model was established by the cecal ligation and puncture (CLP) method. A total of 60 rats were randomized into three groups: a sham group, CLP group, and CLP + LDK378 group (
resultsWe found the group that received LDK378 treatment showed increased MAP levels compared to the CLP group at 30 h and 54 h. Meanwhile, LDK378 ameliorated the perfused small vessel density and microvascular flow index, decreased the expression of TNF-a and IL-6, and upregulated the expression of IL-10 in comparison with the CLP group. LDK378 injections also downregulated the expression of TBK1 and its downstream targets. Furthermore, LDK378 treatment significantly reduced sepsis-induced organ injuries, therefore improving survival rates.
conclusionsThese findings demonstrate that LDK378 treatment can improve microcirculation and reduce organ injuries in CLP-induced septic rats via the regulation of inflammatory cytokine secretion and the downstream signaling components of the ALK-STING pathway.
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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.