Role of peripheral nerve fibres in acute and chronic inflammation in arthritis.

The peripheral nervous system takes an active part in inflammatory processes by regulating effector cell function and reallocation of energy to the immune system. During acute inflammation, rapid neuronal reorganization and change of activity takes place. The hallmarks of this process are an increase in systemic sympathetic activity, a decrease in systemic parasympathetic activity and loss of sympathetic nerve fibres from sites of inflammation concomitant with increased innervation with sensory nerve fibres and increased sensory nerve fibre activity. On a systemic level, the increase in sympathetic activity (and decrease in parasympathetic activity) is necessary to provide enough energy to nourish the activated immune system. In locally inflamed tissue, the decrease in sympathetic nerve fibre density results in reduced anti-inflammatory signalling and, together with neuropeptides released from sensory nerve fibres, promotes local inflammation. In acute inflammation, this 'inflammatory configuration' of the peripheral nervous system favours the rapid clearance of antigenic threats. However, in chronic autoimmune inflammation, these changes of the peripheral nervous system lead to an unfavourable situation with ongoing energy reallocation and continuous local destruction. As an example of a chronic inflammatory condition, we discuss evidence for neuroimmune regulation in autoimmune arthritis with a focus on the sympathetic nervous system.