title: Selective Blocking of TNF Receptor 1 Attenuates Peritoneal Dialysis Fluid Induced Inflammation of the Peritoneum in Mice.
abstract: Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional reorganization of the peritoneal membrane diminishes ultrafiltration rate and thereby enhances mortality by limiting dialysis effectiveness over time. Tumour necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are key players during inflammatory processes. To date, the role of TNFR1 in peritoneal tissue damage during PD-treatment is completely undefined. In this study, we used an acute PD-mouse model to investigate the role of TNFR1 on structural and morphological changes of the peritoneal membrane. TNFR1-mediated TNF signalling in transgenic mice expressing human TNFR1 was specifically blocked by applying a monoclonal antibody (H398) highly selective for human TNFR1 prior to PD-treatment. Cancer antigen-125 (CA125) plasma concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were applied to determine TNFR2 protein concentrations. Histological staining of peritoneal tissue sections was performed to assess granulocytes within the peritoneal membrane as well as the content of hyaluronic acid and collagen. We show for the first time that the number of granulocytes within the peritoneal membrane is significantly reduced in mice pre-treated with H398. Moreover, we demonstrate that blocking of TNFR1 not only influences CA125 values but also hyaluronic acid and collagen contents of the peritoneal tissue in these mice. These results strongly suggest that TNFR1 inhibition attenuates peritoneal damage caused by peritoneal dialysis fluid (PDF) and therefore may represent a new therapeutic approach in the treatment of PD-related side effects.
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kälble
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Damaske
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Danijela
authors.initials: D
authors.lastname: Heide
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Arnold
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Richter
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Maier
authors.affiliation: Department of Molecular Neurobiology, Groningen Institute of Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Eisel
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Scheurich
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfizenmaier
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.|Department of Nephrology, Klinikum Stuttgart, Stuttgart, Germany.
authors.forename: Vedat
authors.initials: V
authors.lastname: Schwenger
authors.affiliation: Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Ranzinger
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D018394:CA-125 Antigen / Q000097:blood; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism* / Q000473:pathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D006820:Hyaluronic Acid; D003094:Collagen