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Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies
07:34

Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies

Published on: April 11, 2012

Antibiotics protect against septic shock in mice administered beta-glucan and indomethacin

Sachiko Nameda1, Noriko N Miura, Yoshiyuki Adachi

  • 1Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Yokyo, Japan.

Microbiology and Immunology
|September 27, 2007
PubMed

Insights

Antibiotics effectively treat sepsis in mice induced by beta-glucan and indomethacin (IND), reducing bacterial translocation and inflammation. However, oral IND administration limits antibiotic efficacy by affecting the gut, highlighting a crucial interaction in sepsis models.

Area of Science:

  • Microbiology
  • Immunology
  • Pharmacology

Background:

  • Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
  • Developing reliable animal models is crucial for understanding sepsis pathogenesis and evaluating therapeutic interventions.
  • Beta-glucan and indomethacin (IND) combination provides a model for sepsis characterized by bacterial translocation and inflammatory responses.

Purpose of the Study:

  • To investigate the therapeutic efficacy of antibiotics in a novel mouse model of sepsis.
  • To elucidate the mechanisms by which antibiotics modulate sepsis-induced inflammation and gut dysfunction.
  • To assess the impact of oral indomethacin administration on antibiotic treatment outcomes in this sepsis model.

Main Methods:

  • Induction of a sepsis model in mice using repeated administration of beta-glucan and indomethacin (IND).
  • Evaluation of antibiotic treatment effects on bacterial translocation, colonic contraction, and inflammatory cytokine production (TNF-alpha, IL-6).
  • Assessment of survival rates and the influence of oral IND administration on antibiotic efficacy.

Main Results:

  • Antibiotic treatment significantly inhibited microbial translocation and colonic contraction.
  • Reduced lipopolysaccharide (LPS)-induced production of TNF-alpha and IL-6 was observed following antibiotic administration.
  • While antibiotics prolonged survival, their efficacy was diminished in mice receiving oral IND, suggesting gut-mediated effects.

Conclusions:

  • Antibiotics demonstrate therapeutic potential in this beta-glucan and IND-induced sepsis model by controlling gut-associated inflammation and bacterial translocation.
  • The route of IND administration significantly influences antibiotic effectiveness, underscoring the importance of the gut microbiome and drug interactions in sepsis.
  • This study provides valuable insights into sepsis pathophysiology and highlights the complex interplay between nonsteroidal anti-inflammatory drugs and antibiotic therapy.

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