Intradialytic cytokine gene expression.

Abstract:

:Along with the numerous technological improvements in molecular biology, polymerase chain reaction, which permits analysis of sequences of a very small amount of biological material, enables evaluation of hemodialysis-induced gene transcription of inflammatory cytokines. Blood samples drawn from 22 hemodialysis patients, treated with cellulose-derived or synthetic membranes, were collected at 0 and 15 min of hemodialysis. Total RNA, purified from mononuclear cells, was reverse transcribed and cDNA amplified by polymerase chain reaction primed with specific oligomers in order to determine tumor necrosis factor alpha (TNF alpha), interleukin (IL) 1 beta and IL6 gene expression. Plasma samples were collected at 0 and 180 min for detection of mature cytokines by enzyme immunoassay with plates pre-coated with monoclonal antibodies to TNF alpha, IL1 beta and IL6. A significant increase in TNF alpha mRNA was detected at 15 min of hemodialysis in 12 of 22 patients: 5 of 9 treated with cuprophan; 3 of 3 with cellulose triacetate; 3 of 5 with polysulfone, and only 1 of 5 treated with polymethyl-methacrylate membranes. A parallel increase in IL1 beta or IL6 mRNA was detected, and significant relationships were found between TNF alpha and IL1 beta (p < 0.001), and IL1 beta and IL6 gene expression (p < 0.05). Increased levels of mature TNF alpha and IL1 beta molecules in plasma were detected in the majority of patients showing an increased cytokine gene expression. However, the absolute amount of cytokine mRNA transcription at 15 min did not predict the levels of mature molecules reached in plasma at 180 min. Cytokine mRNA transcription is quite common at the beginning of a dialysis run. Possibly due to intracellular degradation of critical sequences of cytokine mRNA, gene expression does not necessarily imply translation into mature protein. It is suggested that mechanisms related to cell-to-cell interaction, which may possibly involve procytokine biology, are needed to drive phenomena of cytokine activation to clinical effectiveness.

journal_name

Blood Purif

journal_title

Blood purification

authors

Roccatello D,Menegatti E,Alfieri V,Rossi D,DeLuca A,Pignone E,Mengozzi G,Cesano G,Formica M,Martina G,Sena LM,Piccoli G

doi

10.1159/000014310

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

30-6

issue

1

eissn

0253-5068

issn

1421-9735

pii

bpu16030

journal_volume

16

pub_type

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