ArticleMolecular medicine (Cambridge, Mass.)1997
Lipopolysaccharide-induced cytokine cascade and lethality in LT alpha/TNF alpha-deficient mice.
Article in Molecular medicine (Cambridge, Mass.), 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies.Critical care (London, England) · 2024Pooled it
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- Dual alarmin-receptor-specific targeting peptide systems for treatment of sepsis.Acta pharmaceutica Sinica. B · 2024Article
- Delineation of the distinct inflammatory signaling roles of TAK1 and JAK1/3 in the CIA model of rheumatoid arthritis.Pharmacology research & perspectives · 2023Article
- Cooperation between CYB5R3 and NOX4 via coenzyme Q mitigates endothelial inflammation.Redox biology · 2021Article
- Growth differentiation factor 15 neutralization does not impact anorexia or survival in lipopolysaccharide-induced inflammation.iScience · 2021Article
- Autophagy genes in myeloid cells counteract IFNγ-induced TNF-mediated cell death and fatal TNF-induced shock.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Site-Specific Reprogramming of Macrophage Responsiveness to Bacterial Lipopolysaccharide in Obesity.Frontiers in immunology · 2019Article
- Article
- The triterpenoid CDDO-imidazolide reduces immune cell infiltration and cytokine secretion in the KrasG12D;Pdx1-Cre (KC) mouse model of pancreatic cancer.Carcinogenesis · 2016Article
- The role of TNF-α in rheumatoid arthritis: a focus on regulatory T cells.Journal of clinical and translational research · 2016Review
- FXYD5 Protein Has a Pro-inflammatory Role in Epithelial Cells.The Journal of biological chemistry · 2016Article
- The fiendish behavior of TNF can be counteracted by microRNA.EMBO molecular medicine · 2015Article
- The inflammasome: pathways linking psychological stress, depression, and systemic illnesses.Brain, behavior, and immunity · 2013Review
- Lipopolysaccharide-induced increases in cytokines in discrete mouse brain regions are detectable using Luminex xMAP technology.Journal of neuroscience methods · 2008Article
- Sepsis mediators.Current infectious disease reports · 2007Article
- Tumor Necrosis Factor-alpha- and interleukin-1-induced cellular responses: coupling proteomic and genomic information.Journal of proteome research · 2007Article
- Should we inhibit type I interferons in sepsis?Infection and immunity · 2007Review
- Tissue destruction induced by Porphyromonas gingivalis infection in a mouse chamber model is associated with host tumor necrosis factor generation.Infection and immunity · 2005Article
- Cross-talk between glucocorticoid receptor and AP-1.Oncogene · 2001Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor necrosis factor alpha (TNF-alpha) is often considered the main proinflammatory cytokine induced by lipopolysaccharide (LPS) and consequently the critical mediator of the lethality associated with septic shock. MATERIALS AND
methodsWe used mice carrying a deletion of both the lymphotoxin alpha (LT-alpha) and TNF-alpha genes to assess the role of TNF in the cytokine cascade and lethality induced by LPS.
resultsInitial production of IL-1 alpha, IL-1 beta, IL-6, and IL-10 is comparable in wild-type and mutant mice. However, at later times, expression of IL-1 alpha, IL-1 beta, and IL-10 is prolonged, whereas that of IL-6 decreases in mutant mice. Expression of IFN-gamma is almost completely abrogated in mutants, which is in agreement with a more significant alteration of the late phase of the cytokine cascade. We measured similar LD50 (600 micrograms) for the intravenous injection of LPS in mice of the three genotypes (+/+, +/-, -/-), demonstrating that the absence of TNF does not confer long-term protection from lethality. However, death occurred much more slowly in mutant mice, who were protected more efficiently from death by CNI 1493, an inhibitor of proinflammatory cytokine production, than were wild-type mice. DISCUSSION: Thus, while TNF-alpha is not required for the induction of these cytokines by LPS, it modulates the kinetics of their expression. The lethality studies simultaneously confirm a role for TNF as a mediator of early lethality and establish that, in the absence of these cytokines, other mediators take over, resulting in the absence of long-term protection from LPS toxicity.
Indexed as
Identifiers
9440119PMC2230288W1927790510What 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.