Role of vasoactive intestinal peptide and inflammatory mediators in enteric neuronal plasticity.

Complex circuits involving both local intrinsic neurones (i.e. enteric nervous system; ENS) and extrinsic neurones achieve nervous control of digestive functions. The ENS is comprised of many functionally different types of neurons: sensory neurons, interneurons and secreto-motor neurons. Each neuronal population is required to manifest local reflex behavior and is central to the regulation of both motor and secretory activities. It must be emphasized, however, that not only muscle and secretory cells but also other intestinal cells are targeted by enteric neurones, i.e. endocrine cells, interstitial cells of Cajal, immune cells, blood vessels and enteric glia. In addition to the ENS the gastrointestinal tract receives an extrinsic innervation by sympathetic, parasympathetic and sensory fibres. Neuronal projections from the intestine to prevertebral ganglia also exist. Taken together, the picture of a complex nervous regulation of digestive functions highly integrated with the central nervous system and the rest of the autonomic nervous system has emerged. The ENS is adaptive and plastic, but also vulnerable, system and ENS disturbances may be of pathogenic importance in functional bowel disease. In particular the interplay between the enteric neurones and the immune cells is suggested to be of crucial importance. The review discusses possible roles of the mediators vasoactive intestinal peptide (VIP) and prostanoids in ENS plasticity in response to injury and inflammation

Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice.

VIP is highly expressed in the colon and regulates motility, vasodilatation, and sphincter relaxation. However, its role in the development and progress of colitis is still controversial. Our aim was to determine the participation of VIP on dextran sodium sulfate (DSS)-induced colonic mucosal inflammation using VIP(-/-) and WT mice treated with VIP antagonists. Colitis was induced in 32 adult VIP(-/-) and 14 age-matched WT litter-mates by giving 2.5 % DSS in the drinking water. DSS-treated WT mice were injected daily with VIP antagonists, VIPHyb (n = 22), PG 97-269 (n = 9), or vehicle (n = 31). After euthanasia, colons were examined; colonic cytokines mRNA were quantified. VIP(-/-) mice were remarkably resistant to DSS-induced colitis compared to WT. Similarly, DSS-treated WT mice injected with VIPHyb (1 μM) or PG 97-269 (1 nM) had significantly reduced clinical signs of colitis. Furthermore, colonic expression of IL-1ϐ, TNF-α, and IL-6 was significantly lower in VIP(-/-) and VIPHyb or PG 97-269 compared to vehicle-treated WT. Genetic deletion of VIP or pharmacological inhibition of VIP receptors resulted in resistance to colitis. These data demonstrate a pro-inflammatory role for VIP in murine colitis and suggest that VIP antagonists may be an effective clinical treatment for human inflammatory bowel diseases