Pro inflammatory cytokines and neurogenic inflammation in peritoneal dialysis

Abstract

Master Thesis, Programme in Medicine at University of Gothenburg Title: Pro inflammatory cytokines and neurogenic inflammation in peritoneal dialysis Author: Gustav Engvall, supervised by Magnus Braide Year: 2013 Institution: Institution of Biomedicine at the Sahlgrenska University City: Gothenburg Country: Sweden Introduction: For patients with end stage renal disease (ESRD) peritoneal dialysis (PD) is a widely available and comparatively cheap method to mimic the lost functions of the kidney. However the longevity of the treatment is dependant upon the function of the peritoneal membrane to facilitate the removal of solutes from blood to the dialysate. PD triggers an inflammation, which gradually decreases this function of the peritoneal membrane. Earlier studies have shown expression of various inflammatory cytokines during PD, however the release mechanisms remain unknown. Recently is was shown that PD not only triggers release of pro inflammatory cytokines but also triggers a short neurogenic inflammation with release of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP), through activation of the nociceptor transient receptor potential vanilloid 1 (TRPV1). These neuropeptides are known to induce synthesis of pro inflammatory cytokines. Objectives: Since PD is performed several times daily, neuropeptides are frequently released in to the peritoneal space. The aim of this study was to evaluate the connection between frequent neurogenic inflammations and a sustained, cytokine induced, inflammation. The hypothesis being that inhibition of the TRPV1 receptor decreases the synthesis of pro inflammatory cytokines thereby reducing fibrosis caused by inflammation, leading to a prolonged technique survival in PD. Methods: Rats were subjected to PD with or without preceding i.v. TRPV1- antagonistic treatment (BCTC). After 4 hours of PD, pieces of connective tissue from the diaphragm was excised and homogenized. The mRNA expression of proinflammatory cytokines was measured via qPCR of the homogenate. Results: The obtained data showed no statistic significance supporting the hypothesis.Discussion and Conclusion: Although no significant results could be shown, the rats receiving antagonistic TRPV1 treatment before PD treatment generally showed a lower average expression of pro inflammatory cytokines than the treatment group receiving only PD, suggesting that the TRPV1 treatment was anti-inflammatory. Implications: Since one of the dominating causes of treatment failure in PD is fibrosis due to inflammation, a treatment that reduces inflammation would have great clinical implications. This study could not show data supporting the hypothesis, why the clinical implications become limited. However, the trends seen in this material deserves a closer look in a future study.