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Title: Studies on cytokines and nitric oxide in relation to Cowdria ruminantium infection
Author: Mutunga, Mbithe
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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This thesis describes studies on the pathogenesis of heartwater by investigating the effects of cytokines and nitric oxide (NO) in experimental Cowdria ruminantium infections in in vitro and in vivo models. The latter were carried out in sheep and mice. In sheep infections there were increased levels of antioxidation enzymes, glutathione peroxidase and superoxide dismutase with the highest levels coinciding with the period of the clinical disease. C. ruminantium was also found to induce increased levels of nitrite, indicative of NO, in plasma where the nitrite levels were found to have an earlier and higher increase in sheep with prior exposure to C. ruminantium antigens (immunised and Red Maasai) as compared to naive sheep infections. Mean interferon gamma (IFN-γ) levels in plasma were found to be increased after infection, just prior to or at time of the febrile reaction, with higher levels being recorded in the sheep with prior exposure to C. ruminantium antigens than in the naive animals. There was a gradual increase in mean IL-8 and TNF-α levels after infection and the highest levels coincided with the febrile reaction. Higher levels of IL-8 were recorded in the primary infections than in the sheep with prior exposure. Increased NO is a possible mechanism involved in vasodilatation, and IL-8 in neutrophil activation. However, the increased levels of anti-oxidant enzymes did not support the hypothesis that free radical damage associated with activation of phagocytes occurs in clinical heartwater. NO production was found to be enhanced by bovine recombinant IFN-γ and was inhibited by nitric oxide inducible synthase inhibitor, LNMMA. Induction of apoptotic cell death was seen in IFN-γ treated cells with the infected cells showing higher apoptotic cell death than uninfected cells. Treatment of elementary bodies with NO was found to reduce both infectivity and viability of C. ruminantium. This indicates that NO is released during endothelial infection and has an effect upon infectivity and viability of the organism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available