Serotonin in the Pathogenesis of Lymphocytic Colitis.

Cezary Chojnacki,Tomasz Popławski,Anita Gasiorowska,Jan Chojnacki,Janusz Blasiak

doi:10.3390/jcm10020285

Cezary Chojnacki, Tomasz Popławski + Show 3 more

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https://doi.org/10.3390/jcm10020285

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Abstract

Lymphocytic colitis (LC) is a chronic inflammatory disease associated with watery diarrhea, abdominal pain, and colonic intraepithelial lymphocytosis. Serotonin (5-hydroxytryptamine, 5-HT) is reported to increase in certain colon diseases; however, little is known regarding its metabolism in LC. In the present work, the level of 5-HT in serum and the number of enteroendocrine cells (EECs) as well as the expression of the 5-HT rate-limiting enzyme tryptophan hydroxylase 1 (TPH1) in colonic biopsies and urine 5-hydroxyindoeoacetic acid (5-HIAA) were determined in 36 LC patients that were treated with budesonide and 32 healthy controls. The 5-HT serum and 5-HIAA urine levels were measured using ELISA, the EEC number was determined immunohistochemically, and the colonic TPH1 mRNA expression was determined using RT-PCR. The levels of 5-HT and 5-HIAA and the number of EECs were higher in LC patients than in the controls, and positive correlations were observed between the 5-HT and 5-HIAA levels, 5-HT and EEC number, TPH1 mRNA and EEC number, as well as the severity of disease symptoms and 5-HIAA. Budesonide decreased the levels of 5-HT, 5-HIAA, and TPH1 expression and the number of EECs to values that did not differ from those for controls. In conclusion, the serotonin metabolism may be important for LC pathogenesis, and the urinary level of 5-HIAA may be considered as a non-invasive marker of this disease activity.

Highlights

Lymphocytic colitis (LC), a major subtype of microscopic colitis, is characterized by chronic non-bloody diarrhea, cramping abdominal pain, and other gastrointestinal complaints
The determination of precise number of intraepithelial lymphocytes may be assisted by cluster of differentiation 8 (CD8) and
The serum concentration of C-reactive protein (CRP) was determined by a latex agglutination photometric assay in COBAS INTEGRA 800 (Roche Diagnostic, Basel, Switzerland), the fecal calprotectin (FC) was evaluated by a sandwich ELISA test in Quantum Blue Reader (Buhlmann Diagnostics, Amherst, NH, USA), and the serum serotonin level and urine

Summary

Introduction

Lymphocytic colitis (LC), a major subtype of microscopic colitis, is characterized by chronic non-bloody diarrhea, cramping abdominal pain, and other gastrointestinal complaints (reviewed in [1]). The results showing an increase in EC cells in LC patients inspired us to ask whether that increase was associated with increased 5-HT production and secretion This question is further justified by the fact that 5-HT released from EC cells mediates many functions of the gastrointestinal tract, such as secretion, peristalsis, vasodilation, and the perception of pain, and nausea [14]. This is effectuated by the activation of a disparate family of 5-HT receptors on intrinsic and extrinsic afferent nerve fibers. 5-HT levels in the serum of LC patients, the number of EECs, and the TPH1 expression in the colonic mucosa, as well as the levels of 5-HIAA in the urine of these patients

Patients

Laboratory Tests and Clinical Examinations

Data Analysis

Results

Discussion