ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2014
Determination of the safety and efficacy of therapeutic neutralization of tumor necrosis factor-α (TNF-α) using AZD9773, an anti-TNF-α immune Fab, in murine CLP sepsis.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Neoastilbin ameliorates sepsis-induced liver and kidney injury by blocking the TLR4/NF-κB pathway.Histology and histopathology · 2024Article
- Salidroside protects against intestinal barrier dysfunction in septic mice by regulating IL‑17 to block the NF‑κB and p38 MAPK signaling pathways.Experimental and therapeutic medicine · 2023Article
- Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling.Acta pharmacologica Sinica · 2020Article
- Effect of (-)-α-Bisabolol on the Inflammatory Response in Systemic Infection Experimental Model in C57BL/6 Mice.Inflammation · 2020Article
- LL-37 Exacerbates Local Inflammation in Sepsis-Induced Acute Lung Injury by Preventing Mitochondrial DNA (mtDNA) Degradation-Induced Autophagy.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- A New Venue of TNF Targeting.International journal of molecular sciences · 2018Review
- Sepsis modeling in mice: ligation length is a major severity factor in cecal ligation and puncture.Intensive care medicine experimental · 2016Article
- Deep anesthesia worsens outcome of rats with inflammatory responses.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016Article
- Article
- The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill.Physiological reviews · 2015Review
- Energy crisis: the role of oxidative phosphorylation in acute inflammation and sepsis.Biochimica et biophysica acta · 2014Review
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Authors and funding
10 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
OBJECTIVE AND
designTNF-α neutralization is associated with increased mortality in mouse cecal ligation puncture (CLP) models. AZD9773 is an ovine polyclonal human TNF-α immune Fab, with pharmacological properties that differ from previously studied anti-TNF-α agents. We explored the safety and efficacy of therapeutically administered AZD9773 in mouse CLP sepsis.
methodsA moderate/severe-grade CLP model resulting in 20-30 % 5-day survival and a mild-grade CLP model resulting in ~70 % 5-day survival were established in human TNF-α transgene/murine TNF null (Tg1278/-/-) mice. TREATMENT: Mice received saline resuscitation and imipenem administration every 12 h (0-72 h post-CLP). AZD9773 (or DigiFab control) was dosed 24, 36, 48 and 60 h post-CLP.
resultsTherapeutic dosing of AZD9773 in moderate/severe-grade CLP resulted in significantly increased survival (>70 %) compared with DigiFab (27 %, P < 0.05). Therapeutic dosing of AZD9773 in mild-grade CLP did not significantly affect survival outcome compared with DigiFab or imipenem alone (~60-70 % survival).
conclusionsThese data demonstrate that TNF-α neutralization can improve survival in moderate/severe CLP sepsis. TNF-α suppression in mild-grade models was not associated with survival benefit and did not increase 5-day mortality. These findings suggest that therapeutic benefit following TNF-α attenuation in models of sepsis may depend on model severity.
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