Modulation of leukocyte recruitment in animal models of inflammation in vivo
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Inflammation is an important underlying cause of many chronic diseases, for example in allergic asthma. Glucocorticosteroids provide a powerful anti-inflammatory treatment but are associated with severe side effects when used at high doses for prolonged periods of time; new alternative or adjunct drugs therapies are therefore required. The recruitment of leukocytes to sites of inflammation represents both a key feature of the inflammatory response and a principal source of inflammatory mediators to perpetuate disease. Novel drugs which inhibit leukocyte recruitment or activation may offer a basis for new anti-inflammatory treatments, while early evidence of pharmacological activity in vivo can help prioritise the selection and development of compounds. The present study employed, in controlled experiments, animal models to ascertain in vivo the action of several naturally occurring or synthetic compounds to modulate leukocyte recruitment and to measure any effect they may exert by counting the number of recruited leukocytes (neutrophils or eosinophils) in response to an inflammatory stimuli (used as an objective measure of drug action). Three series of experiments were conducted: one, in a mouse pouch model to test the reaction of differently pre-treated animals to cytokine stimulus; the second, in a guinea-pig model to assess the potentiating effect of pre-treatment to allergen challenge in sensitised animals; thirdly, in the same sensitised guinea-pig model to determine the anti-inflammatory action of a commercially available complementary therapy.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science