Insulin-like Growth Factor-1 Improves Survival in Sepsis via Enhanced Hepatic Bacterial Clearance

Ashare, Alix; Nymon, Amanda B.; Doerschug, Kevin C.; Morrison, John M.; Monick, Martha M.; Hunninghake, Gary W.

doi:10.1164/rccm.200709-1400oc

Cited by 35 publications

(31 citation statements)

References 58 publications

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“…Similar to the portal vein bacterial load, there was evidence of enteric bacteria in the liver at baseline, suggesting the GI tract as the source of these bacteria. We have previously demonstrated that IGF-1 levels are reduced during sepsis (16). Figure 2C demonstrates confirmation that serum IGF-1 levels, as measured by ELISA, are reduced in our murine model of Pseudomonas bacteremia and sepsis.…”

Section: Enteric Bacteremia Is Inversely Correlated With Serum Igf-1 supporting

confidence: 84%

“…This suggests that decreased IGF-1 levels during sepsis likely contribute to the subsequent development of bacterial translocation. Our previous studies showed that IGF-1 treatment also results in decreased organ injury and improved outcome in murine sepsis (16). As a group, these data suggest that one potential mechanism for improved outcome after IGF-1 therapy is decreased bacterial translocation.…”

Section: Enteric Bacteremia Is Inversely Correlated With Serum Igf-1 mentioning

confidence: 74%

“…We have previously demonstrated that IGF-1 levels are reduced in both human sepsis and murine models of sepsis (16). In addition, we demonstrated that treatment with…”

mentioning

confidence: 67%

“…Treatment with IGF-1 decreases GI epithelial cell apoptosis and bacterial translocation in a murine model of severe sepsis. IGF-1 protected mice against organ injury and mortality after a sepsis insult (16). This was true even when the IGF-1 was given 12 hours after the onset of sepsis.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 89%

“…Sepsis was induced in C57BL/6 mice via intratracheal intubation and inoculation, as previously described (16,19,20). Briefly, after anesthesia with ketamine/xylazine, C57BL/6 mice (female, age 6-8 wk; Harlan Laboratories, Indianapolis, IN) underwent intratracheal intubation with a 24-gauge angiocath and infection with Pseudomonas aeruginosa strain PA103 (5 3 10 4 cfu in a 50-ml volume).…”

Section: Pneumonia and Bacteremia Modelmentioning

confidence: 99%

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Insulin-like Growth Factor–1 Levels Contribute to the Development of Bacterial Translocation in Sepsis

Hunninghake¹,

Doerschug²,

Nymon³

et al. 2010

Am J Respir Crit Care Med

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Rationale: Many lines of evidence point toward the gastrointestinal (GI) tract in the pathophysiology of organ dysfunction in sepsis. Splanchnic hypoperfusion during sepsis leads to enterocyte apoptosis, diminished barrier function, and release of bacterial products. Sepsis lowers levels of insulin-like growth factor (IGF)-1, a known antiapoptotic factor. We recently demonstrated that treatment with IGF-1 is protective in murine sepsis. Objectives: We hypothesize that decreased IGF-1 levels in sepsis contributes to the development of bacterial translocation. Methods: Sepsis was induced in C57BL/6 mice via intratracheal instillation of Pseudomonas aeruginosa. Human subjects with sepsis were enrolled if they had a documented positive blood culture with a nonenteric organism. Bacterial translocation was measured in serum by quantitative real-time polymerase chain reaction with primers specific for enteric bacteria. Serum IGF-1 was measured by ELISA. Apoptosis of the GI epithelium was assessed via immunohistochemistry. Measurements and Main Results:We found that mice with severe sepsis had evidence of bacterial translocation by 24 hours. Enteric bacterial load correlated inversely with levels of serum IGF-1. If we treated mice with IGF-1, bacterial translocation was significantly decreased. In addition, we found increased GI epithelial cell apoptosis after sepsis, which was significantly decreased after IGF-1 treatment. Human subjects with nonenteric sepsis developed progressive enteric bacteremia over 3 days. The degree of enteric bacteremia correlated inversely with serum IGF-1 levels. Conclusions: These data support the hypothesis that sepsis-induced reductions in IGF-1 levels contribute to the development of bacterial translocation in both a murine model and human subjects.

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Section: Enteric Bacteremia Is Inversely Correlated With Serum Igf-1 supporting

confidence: 84%

Section: Enteric Bacteremia Is Inversely Correlated With Serum Igf-1 mentioning

confidence: 74%

“…We have previously demonstrated that IGF-1 levels are reduced in both human sepsis and murine models of sepsis (16). In addition, we demonstrated that treatment with…”

mentioning

confidence: 67%

Section: What This Study Adds To the Fieldmentioning

confidence: 89%

Section: Pneumonia and Bacteremia Modelmentioning

confidence: 99%

See 3 more Smart Citations

Insulin-like Growth Factor–1 Levels Contribute to the Development of Bacterial Translocation in Sepsis

Hunninghake¹,

Doerschug²,

Nymon³

et al. 2010

Am J Respir Crit Care Med

Self Cite

View full text Add to dashboard Cite

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Chronic Inflammation in Rheumatoid Arthritis and Mediators of Skeletal Muscle Pathology and Physical Impairment: A Review

Hanaoka

Ithurburn

Rigsbee

et al. 2019

Arthritis Care & Research

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Plasma Proteome Signature of Sepsis: a Functionally Connected Protein Network

et al. 2019

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Sepsis is an extreme host response to infection that leads to loss of organ function and cardiovascular integrity. Mortality from sepsis is on the rise. Despite more than three decades of research and clinical trials, specific diagnostic and therapeutic strategies for sepsis are still absent. The use of LFQ‐ and TMT‐based quantitative proteomics is reported here to study the plasma proteome in five mouse models of sepsis. A knowledge‐based interpretation of the data reveals a protein network with extensive connectivity through documented functional or physical interactions. The individual proteins in the network all have a documented role in sepsis and are known to be extracellular. The changes in protein abundance observed in the mouse models of sepsis have for the most part the same directionality (increased or decreased abundance) as reported in the literature for human sepsis. This network has been named the Plasma Proteome Signature of Sepsis (PPSS). The PPSS is a quantifiable molecular readout that can supplant the current symptom‐based approach used to diagnose sepsis. This type of molecular interpretation of sepsis, its progression, and its response to therapeutic intervention are an important step in advancing our understanding of sepsis, and for discovering and evaluating new therapeutic strategies.

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Insulin-like Growth Factor-1 Improves Survival in Sepsis via Enhanced Hepatic Bacterial Clearance

Abstract: These studies show that the decline in IGF-1 levels in sepsis is related to bacterial clearance and that replacement of IGF-1 in a murine model of sepsis improves overall survival.

Cited by 35 publications

References 58 publications

Insulin-like Growth Factor–1 Levels Contribute to the Development of Bacterial Translocation in Sepsis

Insulin-like Growth Factor–1 Levels Contribute to the Development of Bacterial Translocation in Sepsis

Chronic Inflammation in Rheumatoid Arthritis and Mediators of Skeletal Muscle Pathology and Physical Impairment: A Review

Plasma Proteome Signature of Sepsis: a Functionally Connected Protein Network

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