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Title: Neural regulation of haemopoiesis during acute small intestinal inflammation
Author: Vaddi, Swapna
ISNI:       0000 0004 2719 3404
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2011
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Neural regulation of haemopoiesis has been previously investigated however, the modifications which occur during acute inflammation have not been studied in depth. Therefore we were interested in further understanding the contribution of the nervous system to haemopoiesis. Using the parasitic infection Trichinella spiralis as a model of acute small intestinal inflammation, we were interested in how this immunological challenge would affect the neural regulation of haemopoiesis. Initially we studied the effect of nerve growth factor on bone marrow haemopoeisis. Nerve growth factor is a neurotrophin which has demonstrated an involvement in the regulation of bone marrow haemopoiesis. We found that during Trichinella spiralis infection, rising levels of systemic nerve growth factor inhibited granulopoiesis in the bone marrow, thereby controlling small intestinal inflammation. We hypothesized that a hardwired effect involving innervation of the bone marrow and directed through the brain may counterbalance the antiinflammatory effects of nerve growth factor. Due to previous work on the regulation of inflammation by the cholinergic anti-inflammatory pathway, we hypothesized that the vagus nerve may be involved. Therefore we investigated the effects of a truncal vagotomy on bone marrow haemopoiesis in naïve animals. We found that the vagus nerve is involved in the regulation of myelopoiesis, through hardwired mechanisms which may stimulate the efferent sympathetic input to the bone marrow. On the introduction of Trichinella spiralis infection to this model, we found that the vagus nerve had pro-inflammatory effects in the small intestine as truncal vagotomy reduced small intestinal inflammation during infection, despite increased gut homing innate cells in the bone marrow. This suggested that the vagus nerve modulates the exit of cells from the bone marrow and/or entrance into the intestine. On simulation of vagal stimulation through nicotine treatment, we found that nicotine had pro-inflammatory effects in a Th2 environment, which was detrimental to small intestinal inflammation associated with Trichinella spiralis infection. Our work has shown that bone marrow haemopoiesis is regulated by the nervous system through release of soluble factors and by hardwired mechanisms. Furthermore, these homeostatic mechanisms may be challenged by acute small intestinal infection.
Supervisor: Miyan, Jaleel; Pennock, Joanne Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available