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Updated: May 29, 2026

Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
Pseudomonas aeruginosa is associated with increased lung cytokines and asymmetric dimethylarginine compared with
Linda E Sousse1, Collette C Jonkam, Daniel L Traber
1Department of Anesthesiology, University of Texas Medical Branch, 610 Harborside Drive, Galveston, TX 77555, USA.
Abstract:
The objective of the study was to investigate pulmonary responses to Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) using ovine and mice models of sepsis with emphasis on lung cytokine expression, asymmetric dimethylarginine (ADMA) concentration, and the arginase pathway. Sheep were instilled with either MRSA, P. aeruginosa, or saline under deep anesthesia; mechanically ventilated; resuscitated with fluid; and killed after 24 h. Mice were instilled with either MRSA, P. aeruginosa, or saline under deep anesthesia and killed after 8 h. Lungs were assessed for ADMA concentration, arginase activity, oxidative stress, and cytokine expression, and plasma was assessed for nitrate/nitrite concentrations. The severity of lung injury was more pronounced in P. aeruginosa sepsis compared with MRSA. The significant changes in sheep lung function after P. aeruginosa sepsis were associated with significantly increased ADMA concentrations and arginase activity compared with MRSA. However, the plasma concentration of nitrites and nitrates were significantly increased in MRSA sepsis compared with P. aeruginosa sepsis. In the mice model, P. aeruginosa significantly increased lung cytokine expression (IL-1 and IL-13), protein oxidation, and arginase activity compared with MRSA. Our data suggest that the greater expression of cytokines and ADMA concentrations may be responsible for severity of acute lung injury in P. aeruginosa sepsis. The lack of arginase activity may explain the greater nitric oxide production in MRSA sepsis.
Insights
Pseudomonas aeruginosa sepsis causes more severe lung injury than MRSA sepsis, linked to increased cytokines and ADMA. MRSA sepsis shows higher nitric oxide production due to less arginase activity.
Area of Science:
- Pulmonary Medicine
- Infectious Diseases
- Biochemistry
Background:
- Sepsis-induced acute lung injury (ALI) is a major cause of mortality.
- Different bacterial pathogens may elicit distinct pulmonary responses.
- Understanding these responses is crucial for developing targeted therapies.
Purpose of the Study:
- To compare pulmonary responses to Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) sepsis.
- To investigate lung cytokine expression, asymmetric dimethylarginine (ADMA) concentration, and the arginase pathway in ovine and murine models.
- To elucidate the mechanisms underlying differential severity of lung injury.
Main Methods:
- Ovine and murine models of sepsis were established via intratracheal instillation of P. aeruginosa or MRSA.
- Pulmonary function, lung ADMA concentration, arginase activity, oxidative stress, and cytokine expression were assessed.
- Plasma nitrate/nitrite concentrations were measured.
Main Results:
- P. aeruginosa sepsis induced more severe lung injury than MRSA sepsis in both models.
- P. aeruginosa sepsis was associated with increased lung ADMA and arginase activity.
- MRSA sepsis showed significantly higher plasma nitrite/nitrate concentrations and less arginase activity.
Conclusions:
- Increased cytokine expression and ADMA concentrations contribute to the severity of acute lung injury in P. aeruginosa sepsis.
- Reduced arginase activity in MRSA sepsis may explain the elevated nitric oxide production.
- These findings highlight distinct pathophysiological pathways for different bacterial sepsis types.
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