Gut hormones: emerging role in immune activation and inflammation

Abstract

Gut inflammation is characterized by mucosal recruitment of activated cells from both the innate and adaptive immune systems. In addition to immune cells, inflammation in the gut is associated with an alteration in enteric endocrine cells and various biologically active compounds produced by these cells. Although the change in enteric endocrine cells or their products is considered to be important in regulating gut physiology (motility and secretion), it is not clear whether the change plays any role in immune activation and in the regulation of gut inflammation. Due to the strategic location of enteric endocrine cells in gut mucosa, these gut hormones may play an important role in immune activation and promotion of inflammation in the gut. This review addresses the research on the interface between immune and endocrine systems in gastrointestinal (GI) pathophysiology, specifically in the context of two major products of enteric endocrine systems, namely serotonin (5-hydroxytryptamine: 5-HT) and chromogranins (Cgs), in relation to immune activation and generation of inflammation. The studies reviewed in this paper demonstrate that 5-HT activates the immune cells to produce proinflammatory mediators and by manipulating the 5-HT system it is possible to modulate gut inflammation. In the case of Cgs the scenario is more complex, as this hormone has been shown to play both proinflammatory and anti-inflammatory functions. It is also possible that interaction between 5-HT and Cgs may play a role in the modulation of immune and inflammatory responses. In addition to enhancing our understanding of immunoendocrine interaction in the gut, the data generated from the these studies may have implications in understanding the role of gut hormone in the pathogenesis of both GI and non-GI inflammatory diseases which may lead ultimately to improved therapeutic strategies in inflammatory disorders.

Figures

Fig. 1

Putative role of 5-hyroxytryptophan (5-HT) in immune activation and inflammation. 5-HT released from enterochromaffin cells in response to luminal stimuli (chemical, mechanical or microbial) can act on innate immune cells such as macrophages and dendritic cells to activate proinflammatory cytokine production and can also influence interaction between innate immune and adaptive immune cells to promote inflammation. 5-HT can also act directly on goblet cells to induce mucin production, and on smooth muscle and nerves to alter gut motility.

Fig. 2

Putative role of chromogranins (Cgs) in immune activation and inflammation. Luminal or internal inflammatory stimuli causes alteration in Cgs or Cgs-derived peptides release. They may act locally on paneth, globet and epithelial cells as well as on immune cells, such as macrophages, dendritic cells, neutrophil, mastocytes and eosinophils. Endothelial permeability, chemotaxis, rolling, smooth muscle contractility and the enteric nervous system can also be modulated. IL: interleukin; (−) inhibition; (+) activation.