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Updated: Apr 18, 2026
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Sepsis induced by Staphylococcus aureus: participation of biomarkers in a murine model
Thiago Henrique Caldeira de Oliveira1, Aline Teixeira Amorin1, Izadora Souza Rezende1
1Multidisciplinary Institute of Health, Federal University of Bahia, Vitória da Conquista, Brazil.
Background:
This study aimed to evaluate the role of biomarkers in the pathophysiological process induced by a Staphylococcus aureus strain obtained in a hospital environment. For this, we intraperitoneally inoculated groups of male BALB/c mice with S. aureus, using a clinical isolate (CI) of S. aureus.
Material/Methods:
Mice were divided into groups according to time of euthanasia (24, 48, 72, 96, 120, 144, and 168 hours of infection). After being euthanized, blood samples were collected for quantification of microorganisms and leukocytes, as well as measurement of biomarkers of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-reactive protein (CRP), and Procalcitonin (PCT) by ELISA. Heart, kidneys, and lungs were removed for histopathological analysis, assessment of biomarkers of tissue expression by RT-PCR (polymerase chain reaction with reverse transcriptase), and quantification of microorganisms by real-time quantitative PCR (real-time PCR).
Results:
The animals infected at between 120 hours and 168 hours had the highest blood levels of S. aureus. We observed that infection promoted increases in the levels of circulating neutrophils and monocytes. However, there was a reduction of circulating neutrophils and monocytes after 96 hours of infection. The infected mice also had increased levels of blood lymphocytes. In this model of infection with S. aureus, IL-6, CRP, and PCT demonstrated greater fidelity as markers of infection, since serum levels were elevated and lowered along with the number of circulating neutrophils and monocytes after resolution of the infection. The lungs showed hyperemia, with enlargement of the alveolar septa. On the other hand, infection with S. aureus did not promote visible change in histological tissue in the heart and kidneys.
Conclusions:
In this model of infection with S. aureus, IL-6, CRP, and PCT demonstrated greater fidelity as markers of infection, since serum levels were elevated and lowered along with the number of circulating neutrophils and monocytes after resolution of the infection. We believe our results may provide a better understanding of the pathophysiology, as well as aid in the search for a more reliable method of diagnosis.
Insights
Interleukin-6 (IL-6), C-reactive protein (CRP), and Procalcitonin (PCT) effectively track Staphylococcus aureus infection in mice. These biomarkers correlate with immune cell changes and indicate infection resolution, aiding diagnostic development.
Area of Science:
- Medical Microbiology
- Immunology
- Biomarker Discovery
Background:
- Investigates the pathophysiological effects of a hospital-acquired Staphylococcus aureus strain.
- Utilizes a murine model (BALB/c mice) for infection studies.
Purpose of the Study:
- To evaluate the role of specific biomarkers in Staphylococcus aureus infection.
- To identify reliable indicators of infection and resolution.
Main Methods:
- Intraperitoneal inoculation of mice with S. aureus clinical isolate.
- Monitoring of blood leukocyte counts (neutrophils, monocytes, lymphocytes) over 168 hours.
- Quantification of serum biomarkers (TNF-α, IL-6, CRP, PCT) using ELISA.
- Histopathological analysis of heart, kidneys, and lungs.
- Gene expression analysis of biomarkers via RT-PCR and microbial load via real-time PCR.
Main Results:
- Elevated S. aureus blood levels observed between 120-168 hours post-infection.
- Initial increase in neutrophils and monocytes, followed by a decrease after 96 hours.
- Increased lymphocyte levels detected during infection.
- IL-6, CRP, and PCT showed high correlation with infection dynamics and immune cell counts.
- Pulmonary hyperemia and alveolar septa enlargement observed; heart and kidneys showed no significant histological changes.
Conclusions:
- IL-6, CRP, and PCT are reliable biomarkers for monitoring S. aureus infection progression and resolution in this model.
- These findings enhance understanding of S. aureus pathophysiology.
- The study suggests potential for improved diagnostic methods based on these biomarkers.
