Our immune system is closely related to the axis gut-brain through the enteric nervous system (ENS). Nerves from both the brain and the spinal cord of our colitic or potentially colitic patients interact with structures and substances situated and produced in the bowel wall in both health and in disease. What we feel and what we think, what we hope and what we fear, is communicated to the above-mentioned enteric immune and nervous system and vice versa through the transport of cranial sensation. The ENS consists of hundreds of millions of neurons of four types , each with a specific function. Motor neurons, impinging the bowel muscular layers and the vessels; secretory neurons, triggering exocrine and endocrine functions; interneurons, deputed to the connection among nerve fibres; and sensory neurons, whose den-drites are in the bowel wall originating from neurons in the sacral ganglia and carrying cranial sensation. From a biochemical point of view, the intrinsic gut nerves are of five types: cholinergic, adrenergic, sero-toninergic, gamma-amino-butyric-acid (GABA)ergic and peptidergic - the last being the larger group. A wide variety of peptides have been identified as neurotransmitters in the enteric nervous system .
John Furness is an Australian. He was rather young and enthusiastic, had a reddish curly hair, and when I met him in Adelaide, he took me to visit Flinders University, surrounded by olive trees, on the top of the hill close to the town, which was lying beautifully at the edge of the ocean, like most Australian cities. Marcello Costa left Turin and joined him to carry out outstanding research on intestinal peristalsis. I met him in Rome a few years later when he joined the editorial board of our journal, Techniques in Coloproctology. At that time, I was working with bioengineers and physiologists on a mathematical model of intestinal motor activity in the rabbit colon in vitro .
ENS plays a major role in regulation of secretion, motility, immune function and inflammation in the small and large bowel. Alterations of this regulation are likely to cause GI symptoms in various conditions, including IBD. The immune system and the ENS are integrated in the gut. Galen stated in the second century AD that the emotional state of an individual can cause and, in some case, relieve disease. Immune system alteration was documented in patients suffering from stress, and animals subjected to profound severe stress suffered from immune disturbances such atrophy of lymph nodes and consequently developed intestinal ulcers.
Psychological stress influence immune function, and it has been demonstrated that lymphoid tissue is directly innervated. Secretory products of the immune system, which include interleukins and neu-ropeptides, may also influence the neuroendocrine system. Communication between the two systems is therefore bidirectional . Lymphocyte function is altered by ENS neuropeptides, such as somatostatin. Conversely, endocrine products of the immune system, such interleukin (IL)-1, have an effect on the gut. In IBD, vasoactive intestinal polypeptide (VIP)ergic neurons are prominent immunohistochemically, and concentrations of rectal mucosal VIP are elevated . Patients with IBD have elevated circulating and mucosal cytokine production . Lymphokines and immunotransmitters seem to transfer information from the immune centres to the brain .
Put together, these findings suggest, but do not prove, that the pathophysiology of IBD may be related to alterations in immune ENS and gut-brain interactions, resulting in inflammation and diarrhoea . Further clarification of the underlying patho-physiologic derangements offer hope for specific therapeutic intervention focused on the PNEI-G system .
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