Correlation between CgA and TNF receptor-I (TNFR-I) and TNFR-II has been evaluated in patients before the initiation of treatment with Infliximab® and compared it with the value calculated selleck compound during treatment . The authors observed a high correlation between
CgA and both receptors. Moreover, they found that treatment with anti-TNF-α monoclonal antibodies (mAbs) abrogated the correlation between CgA and TNFR-I and TNFR-II, but it should be mentioned that in this study anti-TNF-α mAbs treatment did not modify the mean levels of CgA and TNFRs but led only to the abrogation of the correlation between CgA and TNFRs, implying that perhaps other indirect factors are associated in this effect. Three years later, the same group described that patients with RA have significantly higher serum levels of CgA
and TNFRs compared with controls and that the highest levels of CgA identify the population of patients with extra-articular manifestations . Taken together, these results suggest that CgA might be involved in the pathogenesis of inflammatory autoimmune disease through a complex interaction with TNF-α, mediated by as yet-undefined factors. In a series of papers Metz-Boutigue’s group, who have published extensively on granins, showed a link between serum concentration of CgA and outcome in patients admitted with or without systemic PD98059 molecular weight inflammatory response syndrome. CgA concentrations were correlated positively with inflammation markers such as procalcitonin and C-reactive protein, but also with simplified acute physiological score (SAPS). A Cox Orotidine 5′-phosphate decarboxylase model confirmed that CgA and SAPS were independent predictors of outcome [75,76]. In addition, a significant association has been reported between CgA level and periodontitis, again
showing a close relationship between the level of CgA and the inflammatory process . The hypothesis that Cgs-derived peptides are involved in mechanisms modulating altered colonic motility and visceral pain induced by gut inflammation was tested for the first time in 2004 using an application of acetic acid (AA) in vitro and in vivo. Using the writhing test, a model of somato-visceral pain, we have demonstrated that depending upon the Cgs-derived peptides used (bCgA 4–16, 47–66), they could display pro- and anti-nocicpetive effects [78,79]. In the context of smooth muscle contraction, Cgs-derived peptides modulate the effect of AA on human and rat smooth muscle contraction via a direct action on the calcium L-type channel or towards an indirect action through the enteric nervous system (motorneurone and type-C sensitive fibre) [80,81]. All these data provide proof of concept that Cgs and Cgs-derived peptides seem to play an important role in the development of inflammatory pathologies, and different groups have now focused their attention upon characterizing a mechanistic explanation. The studies discussed in this review provide evidence in favour of a key role of gut hormones in intestinal inflammation.