Trial reportClinical and experimental immunology2001
Suppression of the clinical and cytokine response to endotoxin by RWJ-67657, a p38 mitogen-activated protein-kinase inhibitor, in healthy human volunteers.
Trial report in Clinical and experimental immunology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 101 citations in OpenAlex.
- POLB 001, a p38 MAPK inhibitor, decreases local and systemic inflammatory responses followingFrontiers in immunology · 2025Trial
- Time course of angiopoietin-2 release during experimental human endotoxemia and sepsis.Critical care (London, England) · 2009Trial
- Identification of Imidazole-Benzenesulfonamide Derivatives with Anti-Inflammatory Activity Through Modulation of NF-κB Signaling.Molecules (Basel, Switzerland) · 2026Article
- Bacterial extracellular vesicles repress the vascular protective factor RNase1 in human lung endothelial cells.Cell communication and signaling : CCS · 2023Article
- Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury.Nature reviews. Nephrology · 2022Review
- Unlocking the Untapped Potential of Endothelial Kinase and Phosphatase Involvement in Sepsis for Drug Treatment Design.Frontiers in immunology · 2022Review
- Small molecules to the rescue: Inhibition of cytokine signaling in immune-mediated diseases.Journal of autoimmunity · 2017Review
- Central nervous system circuits modified in heart failure: pathophysiology and therapeutic implications.Heart failure reviews · 2014Review
- The adenosine A₂A receptor - myocardial protectant and coronary target in endotoxemia.International journal of cardiology · 2013Article
- Review
- Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia.Experimental & translational stroke medicine · 2012Article
- Subtoxic levels hydrogen peroxide-induced production of interleukin-6 by retinal pigment epithelial cells.Molecular vision · 2010Article
- Differential effects of p38MAP kinase inhibitors on the expression of inflammation-associated genes in primary, interleukin-1beta-stimulated human chondrocytes.British journal of pharmacology · 2010Article
- The protein C pathway and pathologic processes.Journal of thrombosis and haemostasis : JTH · 2009Review
- SD0006: a potent, selective and orally available inhibitor of p38 kinase.Pharmacology · 2009Article
- Update on Targets of Biologic Therapies for Rheumatoid Arthritis.Current rheumatology reviews · 2008Article
- A potent and selective p38 inhibitor protects against bone damage in murine collagen-induced arthritis: a comparison with neutralization of mouse TNFalpha.British journal of pharmacology · 2008Article
- p38 mitogen-activated protein kinase inhibition decreases TNFalpha secretion and protects against left ventricular remodeling in rats with myocardial ischemia.Inflammation · 2008Article
- Mitogen activated protein kinase inhibitors: where are we now and where are we going?Annals of the rheumatic diseases · 2006Review
- The p38 mitogen-activated protein kinase signaling cascade in CD4 T cells.Arthritis research & therapy · 2006Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledSepsis resulting in multiorgan failure and death is still a major problem in intensive care medicine, despite extensive attempts to interfere in the supposed underlying mechanism of a deranged immune system. This is not only due to the persistent lacunae in knowledge about the immune system in sepsis but also due to the lack of sufficient instruments for intervention. Inhibitors of the p38 mitogen-activated protein kinase (p38MAPK) have been used to study the signalling pathway of the immune response. In vitro and animal studies have demonstrated that blocking p38MAPK could mitigate the pro-inflammatory response and improve survival after endotoxaemia. Using an endotoxaemia model in healthy human volunteers we evaluated the attenuation of clinical and cytokine response to endotoxin after inhibition of p38MAPK by an oral dose of RWJ-67657, a pyrindinyl imidazole. We measured the clinical parameters temperature, blood pressure and heart rate. The proinflammatory cytokines tumour necrosis factor-alpha, interleukin-6 and interleukin-8 were measured by ELISA at various points during a 24-h period. Drug toxicity was evaluated by routine clinical and laboratory examinations. After a single dose dose of RWJ-67657 the temperature and blood pressure response remained at the basal level. The inhibition of TNF-alpha, IL-6 and IL-8 response was a dose dependent. With the maximum dosage, reduction in peak serum levels of the proinflammatory cytokines was greater than 90%. There was no drug-related toxicity.
interpretationWe conclude that inhibition of p38MAPK by RWJ-67657 might be a tool to intervene in the deranged immune response in sepsis and other inflammatory diseases.
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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.