ArticleNeurogastroenterology and motility2012
Role of interleukin-6 in hemopoietic and non-hemopoietic synergy mediating TLR4-triggered late murine ileus and endotoxic shock.
Article in Neurogastroenterology and motility, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Establishment of an inflammatory cytokine-based predictive model for the onset of prolonged postoperative ileus after radical gastrectomy: a prospective cohort study.Frontiers in immunology · 2025Article
- The Role of Inflammatory Mediators in the Development of Gastrointestinal Motility Disorders.International journal of molecular sciences · 2022Review
- Resveratrol enhances vascular reactivity in mice following lipopolysaccharide challenge via the RhoA-ROCK-MLCP pathway.Experimental and therapeutic medicine · 2017Article
- Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients.Gastroenterology research and practice · 2016Article
- Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundEarly murine endotoxin-induced ileus at 6 h is exclusively mediated by non-hemopoietic TLR4/MyD88 signaling despite molecular activation of hemopoietic cells which included a significant IL-6 mRNA induction. Our objective was to define the role of hemopoietic cells in LPS/TLR4-triggered ileus and inflammation over time, and identify mechanisms of ileus.
methodsCSF-1(-/-) , TLR4 non-chimera and TLR4 chimera mice were single-shot intraperitoneal injected with ultrapure lipopolysaccharide (UP-LPS) and studied up to 4 days. Subgroups of TLR4(WT) mice were additionally intravenously injected with exogenous recombinant IL-6 (rmIL-6) or murine soluble IL-6 receptor blocking antibody (anti-sIL-6R mAB). KEY
resultsHemopoietic TLR4 signaling independently mediated UP-LPS-induced ileus at 24 h, but chemotactic muscularis neutrophil extravasation was not causatively involved and mice lacking CSF-1-dependent macrophages died prematurely. Synergy of hemopoietic and non-hemopoietic cells determined ileus severity and mortality which correlated with synergistic cell lineage specific transcription of inflammatory mediators like IL-6 within the intestinal muscularis. Circulating IL-6 levels were LPS dose dependent, but exogenous rmIL-6 did not spark off a self-perpetuating inflammatory response triggering ileus. Sustained therapeutic inhibition of functional IL-6 signaling efficiently ameliorated late ileus while preemptive antibody-mediated IL-6R blockade was marginally effective in mitigating ileus. However, IL-6R blockade did not prevent endotoxin-associated mortality nor did it alter circulating IL-6 levels. CONCLUSIONS & INFERENCES: A time-delayed bone marrow-driven mechanism of murine endotoxin-induced ileus exists, and hemopoietic cells synergize with non-hemopoietic cells thereby prolonging ileus and fueling intestinal inflammation. Importantly, IL-6 signaling via IL-6R/gp130 drives late ileus, yet it did not regulate mortality in endotoxic shock.
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