Related Experiment Video
Updated: Jun 7, 2026
Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
Published on: February 23, 2014
Recombinant human tissue factor pathway inhibitor exerts anticoagulant, anti-inflammatory and antimicrobial effects
F E Van Den Boogaard1, X Brands, M J Schultz
1Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, the Netherlands. f.e.vandenboogaard@amc.uva.nl
Background:
Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia and a major cause of sepsis. Recombinant human tissue factor pathway inhibitor (rh-TFPI) attenuates sepsis-induced coagulation and has been evaluated in clinical trials involving patients with sepsis and community-acquired pneumonia.
Objective:
To examine the effect of rh-TFPI on coagulation, inflammation and bacterial outgrowth in S. pneumoniae pneumonia in mice, with or without concurrent antibiotic treatment.
Methods:
Pneumonia was induced by intranasal inoculation with S. pneumoniae. Mice were treated with placebo, rh-TFPI, ceftriaxone or rh-TFPI combined with ceftriaxone. Early (8 h) and late (24 h) initiated treatments were evaluated. Samples were obtained 24 or 48 h after infection, for early and late initiated treatment, respectively. In vitro, placebo or rh-TFPI was added to a suspension of S. pneumoniae.
Results:
Rh-TFPI reduced pneumonia-induced coagulation; rh-TFPI with ceftriaxone further attenuated coagulation relative to ceftriaxone alone. Rh-TFPI inhibited accumulation of neutrophils in lung tissue and reduced the levels of several cytokines and chemokines in lungs and plasma in mice not treated with antibiotics; in these animals, rh-TFPI initiated 24 h after infection decreased pulmonary bacterial loads. In vitro, rh-TFPI also inhibited growth of S. pneumoniae.
Conclusions:
Therapeutic rh-TFPI attenuates coagulation, inflammation and bacterial growth during pneumococcal pneumonia, whereby the latter two effects only become apparent in the absence of concurrent antibiotic treatment.
Insights
Recombinant human tissue factor pathway inhibitor (rh-TFPI) reduces coagulation, inflammation, and bacterial growth in Streptococcus pneumoniae pneumonia. These benefits are most apparent when rh-TFPI is used without antibiotics.
Area of Science:
- Biomedical research
- Infectious disease
- Pharmacology
Background:
- Streptococcus pneumoniae is a leading cause of pneumonia and sepsis.
- Recombinant human tissue factor pathway inhibitor (rh-TFPI) has shown potential in treating sepsis and pneumonia.
Purpose of the Study:
- To investigate the impact of rh-TFPI on coagulation, inflammation, and bacterial growth in S. pneumoniae pneumonia in a mouse model.
- To assess these effects with and without concurrent antibiotic treatment.
Main Methods:
- Pneumonia was induced via intranasal S. pneumoniae inoculation in mice.
- Mice received placebo, rh-TFPI, ceftriaxone, or a combination of rh-TFPI and ceftriaxone.
- In vitro studies assessed rh-TFPI's effect on S. pneumoniae growth.
Main Results:
- rh-TFPI mitigated pneumonia-induced coagulation, with combined therapy showing enhanced effects.
- rh-TFPI reduced neutrophil accumulation and inflammatory markers in lungs and plasma in non-antibiotic treated mice.
- rh-TFPI treatment, initiated later, decreased bacterial load in the lungs and inhibited bacterial growth in vitro.
Conclusions:
- Therapeutic rh-TFPI effectively reduces coagulation, inflammation, and bacterial growth in pneumococcal pneumonia.
- Anti-inflammatory and anti-bacterial effects of rh-TFPI are most evident in the absence of antibiotics.
More Related Videos
12:21A Mouse Model for the Transition of Streptococcus pneumoniae from Colonizer to Pathogen upon Viral Co-Infection Recapitulates Age-Exacerbated Illness
Published on: September 28, 2022
13:45A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
Published on: September 21, 2019