Characterisation of the acute inflammation during murine pneumococcal pneumonia

Kerr, Alison Russell (2000) Characterisation of the acute inflammation during murine pneumococcal pneumonia. PhD thesis, University of Glasgow.

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We have established a murine model of pneumococcal pneumonia in order to characterise the host inflammatory response. Intranasal infection with Streptococcus pneumoniae resulted in constant bacterial loads within airways of susceptible mouse strains whilst the pathogen burden increased in both the lung tissues and bloodstream. The bacteria induced inflammation that was evident as perivascular cell recruitment in histological sections. Mast cell granule staining indicated that this population degranulated early in the inflammatory response, releasing TNFa into the lung environment. Levels of TNFa and IL-1b increased during mid infection with release of IL-6 and the anti-inflammatory cytokine IL-10 not occurring until late infection. Kinetics of IL-10 were too slow to prevent inflammation causing damage to the host tissues. The total protein levels in bronchoalveolar lavage fluid (a marker of the integrity of the alveolar/capillary barrier) increased significantly during the experiment. Dose response results indicate that there is likely to be a threshold number of bacteria required to induce this inflammatory response both in the lungs and bloodstream. Inoculation of bacteria into a mouse strain resistant to the above infection resulted in bacterial clearance from both the pulmonary airways and tissues, with few more becoming bacteraemic. The location and timing of the inflammatory response in this mouse strain was significantly different. Inflammatory cell influx occurred mainly within the airways, with perivascular areas unaffected. Mast cell degranulation occurred rapidly following infection. TNF activity and IL-1b levels within lung airways were induced earlier and to a greater extent than in susceptible mice. IN contrast, the levels of TNF activity and IL-6 within lung tissues were lower in resistant mice. Although damage to lung integrity still occurred, this was only transient and evident during early/mid infection.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Supervisor's Name: Supervisor, not known
Date of Award: 2000
Depositing User: Ms Mary Anne Meyering
Unique ID: glathesis:2000-6241
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 31 Mar 2015 14:52
Last Modified: 31 Mar 2015 15:18

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