Human parainfluenza viruses (PIV) 1, 2, 3 and 4 (A and B) cause approximately 39-40% of all acute respiratory infections in infants and children for which there is no effective therapy. Firstly, this thesis was aimed at ascertaining a suitable guinea pig model of PIV-3 infection by determining the most efficient route of virus application. Secondly, to ascertain if a temporal association may be established during the time course of infection (Day 1-40) by measuring the following parameters: body weight, rectal temperature, airway function (sGaw), airways reactivity to inhaled histamine, inflammatory cell infiltration to the lungs measured by bronchoalveolar lavage, wet lung weights, inflammatory markers (nitric oxide and total protein levels), lung histological analysis and recovery of the virus from bronchoalveolar lavage fluid and lung tissue. Further to this, experiments were also designed to determine the impact of the glucocorticoid, dexsamethasone (in vivo and in vitro) and the phosphodiesterase inhibitor, rolipram (in vivo). Lastly, this study ascertained the effect of pre-sensitisation with antigen on the responses of antigen in PIV-3 infected guinea pigs. These investigations have shown guinea pigs to be a suitable model for PIV-3 infection and intranasal inoculation is the most efficient route of virus application. In addition, these investigations also established a temporal association between the time course of PIV-3 infection including airway reactivity to histamine, airway function (sGBW), airways reactivity to inhaled histamine, inflammatory cell infiltration, wet lung weights, inflammatory markers (nitric oxide and total protein levels), pulmonary histopathology and recovery of the virus from bronchoalveolar lavage fluid and lung tissue. Pre-treatment of PIV-3 infected guinea pigs with the glucocorticoid, dexamethasone and the phosphodiesterase inhibitor, rolipram (in vitro) ameliorated the inflammatory response and airway hyperreactivity. Unlike rolipram, dexamethasone also reduced viral titre (in vivo and in vitro), supporting a role for the anti-viral effects of dexamethasone. The anti-inflammatory effects of dexamethasone are well known and it has been speculated by other authors which maybe caused by decreased viral receptors on the epithelial cells via inhibition of intracellular adhesion molecule-1 expression. Finally, in this study PTV-3 infection, enhanced the effect of pre-allergen sensitisation, which may arise from increased permeability of the airway mucosa to allergens, due to damage of the respiratory epithelium and increased recruitment of dendritic cells. In summary, this thesis has established a clearly defined efficacy of dexamethasone use in the treatment of PIV-3 infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:584153 |
| Date | January 2007 |
| Creators | Chidgey, Sharon Michelle |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/55663/ |
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