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SUMMARY
The nervous system in the intestine controls motility, secretion, sensory perception, and immune function. Peptidergic neurones with neurotransmitters such as substance P and nerve growth factors have been the main focus of neuroimmunomodulation research in the gut. This review summarises the present knowledge concerning the role of the sympathetic nervous system (SNS) in modulating intestinal inflammation. The role of the SNS for gut inflammation is compared with its role in rheumatoid arthritis which demonstrates notable similarities. Nerve fibres of the SNS not only enter the enteric plexuses but also innervate the mucosa and gut associated lymphoid tissue (GALT). The SNS has pro- and anti-inflammatory functions. Neurotransmitters such as norepinephrine, adenosine, and others can evoke remarkably different opposing effects depending on concentration (presence of sympathetic nerve fibres and extent of neurotransmitter release), receptor affinity at different receptor subtypes, expression of adrenoceptors, availability of cotransmitters, and timing of SNS activity in relation to the inflammatory course. This review attempts to integrate the different perspectives of the pro- and anti-inflammatory effects of the SNS on inflammatory disease of the gut.
INTRODUCTION
Since the work of Selye in the 1940s, the SNS together with the hypothalamic-pituitary-adrenal (HPA) axis was thought to play an important supportive role in the fight and flight reaction during stressful situations (fig 1⇓).1 In linking this important concept to inflammatory diseases, several groups, from 1960 to the late 1980s, delineated the proinflammatory role of the SNS for the early inflammatory response (fig 1⇓) (for example, see Levine and colleagues2). Indeed, the SNS is a critical proinflammatory component of neurogenic inflammation, which is particularly evident during the first hours of induction of inflammation.3 This is most probably due to the supportive effects of neurotransmitters on plasma extravasation and directed migration of immune cells to sites of …