Neural regulation of haemopoiesis has been previously investigated however,the modifications which occur during acute inflammation have not been studiedin depth. Therefore we were interested in further understanding thecontribution of the nervous system to haemopoiesis. Using the parasiticinfection Trichinella spiralis as a model of acute small intestinal inflammation,we were interested in how this immunological challenge would affect the neuralregulation of haemopoiesis.Initially we studied the effect of nerve growth factor on bone marrowhaemopoeisis. Nerve growth factor is a neurotrophin which has demonstratedan involvement in the regulation of bone marrow haemopoiesis. We found thatduring Trichinella spiralis infection, rising levels of systemic nerve growth factorinhibited granulopoiesis in the bone marrow, thereby controlling small intestinalinflammation.We hypothesized that a hardwired effect involving innervation of the bonemarrow and directed through the brain may counterbalance the antiinflammatoryeffects of nerve growth factor. Due to previous work on theregulation of inflammation by the cholinergic anti-inflammatory pathway, wehypothesized that the vagus nerve may be involved. Therefore we investigatedthe effects of a truncal vagotomy on bone marrow haemopoiesis in naïveanimals. We found that the vagus nerve is involved in the regulation ofmyelopoiesis, through hardwired mechanisms which may stimulate the efferentsympathetic input to the bone marrow. On the introduction of Trichinella spiralisinfection to this model, we found that the vagus nerve had pro-inflammatoryeffects in the small intestine as truncal vagotomy reduced small intestinalinflammation during infection, despite increased gut homing innate cells in thebone marrow. This suggested that the vagus nerve modulates the exit of cellsfrom the bone marrow and/or entrance into the intestine.On simulation of vagal stimulation through nicotine treatment, we found thatnicotine had pro-inflammatory effects in a Th2 environment, which wasdetrimental to small intestinal inflammation associated with Trichinella spiralisinfection.Our work has shown that bone marrow haemopoiesis is regulated by thenervous system through release of soluble factors and by hardwiredmechanisms. Furthermore, these homeostatic mechanisms may be challengedby acute small intestinal infection.
|Date of Award||31 Dec 2011|
- The University of Manchester
|Supervisor||Jaleel Miyan (Supervisor) & Joanne Pennock (Supervisor)|