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Sepsis induced by Staphylococcus aureus: participation of biomarkers in a murine model.

de Oliveira TH, Amorin AT, Rezende IS, Santos Barbosa M, Martins HB, Brito AK, Andrade EF, Gonçalves GK, Campos GB, Silva RA, Timenetsky J, Marques LM - Med. Sci. Monit. (2015)

Bottom Line: However, there was a reduction of circulating neutrophils and monocytes after 96 hours of infection.On the other hand, infection with S. aureus did not promote visible change in histological tissue in the heart and kidneys.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.

View Article: PubMed Central - PubMed

Affiliation: Multidisciplinary Institute of Health, Federal University of Bahia, Vitória da Conquista, Brazil.

ABSTRACT

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.

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Gene expression of CRP in BALB/c mice infected for 7 days with clinical isolate strain of S. aureus in heart (A), kidneys (B), and lungs (C). Infected animals showed significant increases in gene expression of CRP in the heart within 24 hours of infection, and 48 hours in the kidneys and lungs. Electrophoresis represents the gene expression profile obtained from lung tissue. *** p<0.05 vs. saline.
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f6-medscimonit-21-345: Gene expression of CRP in BALB/c mice infected for 7 days with clinical isolate strain of S. aureus in heart (A), kidneys (B), and lungs (C). Infected animals showed significant increases in gene expression of CRP in the heart within 24 hours of infection, and 48 hours in the kidneys and lungs. Electrophoresis represents the gene expression profile obtained from lung tissue. *** p<0.05 vs. saline.

Mentions: To study the mechanisms involved in the different response times of infection, we analyzed serum levels of TNF-α, IL-6, PCT, and CRP by ELISA after infection with S. aureus. In infected animals, the serum levels of biomarkers increased in direct relation to the time of infection. The increase in serum was more significant with respect to IL-6 (Figure 3A), CRP (Figure 3C), and PCT (Figure 3D) compared to the control group. A borderline significant correlation was observed in TNF-α dosages (Figure 3B). Infected animals showed an increased expression of IL-6 in the heart within 48 hours of infection (Figure 4A). In the kidney, the increase was more evident at 96 hours (Figure 4B), and in the lung there was a more pronounced increase of IL-6 at 72 hours of infection (Figure 4C). There was a significant increase in the expression of PCT, which was more evident within 96 hours of infection in the heart (Figure 5A), kidney (Figure 5B) and lung (Figure 5C). Infected animals also showed significant increases in gene expression of CRP in the heart within 24 hours of infection (Figure 6A), and 48 hours in the kidney (Figure 6B) and lung (Figure 6C), as well as an increased gene expression of TNF-α between 48 and 72 hours of infection in the heart (Figure 7A), kidney (Figure 7B), and lung (Figure 7C). 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.


Sepsis induced by Staphylococcus aureus: participation of biomarkers in a murine model.

de Oliveira TH, Amorin AT, Rezende IS, Santos Barbosa M, Martins HB, Brito AK, Andrade EF, Gonçalves GK, Campos GB, Silva RA, Timenetsky J, Marques LM - Med. Sci. Monit. (2015)

Gene expression of CRP in BALB/c mice infected for 7 days with clinical isolate strain of S. aureus in heart (A), kidneys (B), and lungs (C). Infected animals showed significant increases in gene expression of CRP in the heart within 24 hours of infection, and 48 hours in the kidneys and lungs. Electrophoresis represents the gene expression profile obtained from lung tissue. *** p<0.05 vs. saline.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4321564&req=5

f6-medscimonit-21-345: Gene expression of CRP in BALB/c mice infected for 7 days with clinical isolate strain of S. aureus in heart (A), kidneys (B), and lungs (C). Infected animals showed significant increases in gene expression of CRP in the heart within 24 hours of infection, and 48 hours in the kidneys and lungs. Electrophoresis represents the gene expression profile obtained from lung tissue. *** p<0.05 vs. saline.
Mentions: To study the mechanisms involved in the different response times of infection, we analyzed serum levels of TNF-α, IL-6, PCT, and CRP by ELISA after infection with S. aureus. In infected animals, the serum levels of biomarkers increased in direct relation to the time of infection. The increase in serum was more significant with respect to IL-6 (Figure 3A), CRP (Figure 3C), and PCT (Figure 3D) compared to the control group. A borderline significant correlation was observed in TNF-α dosages (Figure 3B). Infected animals showed an increased expression of IL-6 in the heart within 48 hours of infection (Figure 4A). In the kidney, the increase was more evident at 96 hours (Figure 4B), and in the lung there was a more pronounced increase of IL-6 at 72 hours of infection (Figure 4C). There was a significant increase in the expression of PCT, which was more evident within 96 hours of infection in the heart (Figure 5A), kidney (Figure 5B) and lung (Figure 5C). Infected animals also showed significant increases in gene expression of CRP in the heart within 24 hours of infection (Figure 6A), and 48 hours in the kidney (Figure 6B) and lung (Figure 6C), as well as an increased gene expression of TNF-α between 48 and 72 hours of infection in the heart (Figure 7A), kidney (Figure 7B), and lung (Figure 7C). 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.

Bottom Line: However, there was a reduction of circulating neutrophils and monocytes after 96 hours of infection.On the other hand, infection with S. aureus did not promote visible change in histological tissue in the heart and kidneys.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.

View Article: PubMed Central - PubMed

Affiliation: Multidisciplinary Institute of Health, Federal University of Bahia, Vitória da Conquista, Brazil.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus