Down-regulation of inflammatory signaling pathways despite up-regulation of Toll-like receptors; the effects of corticosteroid therapy in brain-dead kidney donors, a double-blind, randomized, controlled trial

Jafari, R. and Aflatoonian, R. and Falak, R. and Pourmand, G. and Dehghani, S. and Mortazavi, M. and Adelipour, A. and Rezaei, A. and Tajik, N. (2018) Down-regulation of inflammatory signaling pathways despite up-regulation of Toll-like receptors; the effects of corticosteroid therapy in brain-dead kidney donors, a double-blind, randomized, controlled trial. Molecular Immunology, 94. pp. 36-44.

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Abstract

Background The brain death of a potential organ donor induces a systemic inflammatory response, resulting in inferior organ quality and function. Our study aimed to evaluate the effects of methylprednisolone (MPN) therapy on pattern recognition receptor (PRR) signaling in potential brain-dead (BD) kidney donors. Material and methods To evaluate the effects of MPN therapy on PRR signaling in BD kidney donors we performed a prospective randomized treatment-versus-control study. Fifty-one potential kidney donors were randomly divided into three groups: brain-dead donors (BDDs) who received 15 mg/kg/d of methylprednisolone (group T1, n = 17), BDDs who received 15 mg/kg/d of MPN at the time of filling consent for kidney donation and 100 mg/2 h until kidney harvest (group T2, n = 17), and normal donors as controls n = 17. Gene expression for Toll-like receptors (TLRs) 1�9 and their signaling pathway molecules including MYD88, TRIF, NF-KB1, IRAK, IRF3, and IRF7, as well as the inflammatory cytokines RANTES, IL-1β TNF-α IL-6, CXCL8, IL-18, IFN-α and IFN-β was determined by PCR array. Due to the crucial role of TLRs 2 and 4 in pattern recognition, surface expression of these molecules was analyzed by flow cytometry. Plasma levels of inflammatory cytokines were measured by immunoassay. Finally, serum creatinine and cystatin C were measured in 100 kidney recipients one week and one, three, and six months after transplant. Result Polymerase chain reaction (PCR) array gene expression revealed greater expression of TLRs and signaling molecules in group T1 than in the controls. Surface expression of TLRs 2 and 4 were significantly greater in group T2 than in group T1 (P <.05). Plasma concentrations of inflammatory cytokines were significantly greater in group T1 than in controls (P <.05). The recipients that received kidneys from group T1 had significantly higher levels of creatinine and cystatin C than the recipients of kidneys from both group T1 and controls (P<0.05). Conclusion Administration of MPN to BDDs at specified periods until kidney harvest resulted in less systemic inflammation in the BDDs and improved renal function in kidney graft recipients compared with common MPN therapy. © 2017 Elsevier Ltd

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: alpha interferon; beta interferon; creatinine; cystatin C; immunoglobulin enhancer binding protein; interferon regulatory factor 3; interferon regulatory factor 7; interleukin 1 receptor associated kinase; interleukin 18; interleukin 1beta; interleukin 6; interleukin 8; methylprednisolone; myeloid differentiation factor 88; pattern recognition receptor; RANTES; toll like receptor; toll like receptor 1; toll like receptor 2; toll like receptor 3; toll like receptor 4; toll like receptor 5; toll like receptor 6; toll like receptor 7; toll like receptor 8; toll like receptor 9; toll like receptor adaptor molecule 1, adult; Article; brain death; clinical article; clinical evaluation; controlled study; corticosteroid therapy; creatinine blood level; double blind procedure; down regulation; drug effect; female; flow cytometry; gene expression; graft recipient; human; immunoassay; kidney donor; male; organ donor; polymerase chain reaction; priority journal; randomized controlled trial; signal transduction; surface property; upregulation
Subjects: WJ Urogenital System
QV Pharmacology
Depositing User: eprints admin
Date Deposited: 25 Dec 2018 16:12
Last Modified: 21 Aug 2019 05:45
URI: http://eprints.iums.ac.ir/id/eprint/6109

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