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      Intradialytic Cytokine Gene Expression

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          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 α (TNFα), interleukin (IL) 1β 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 TNFα, IL1β and IL6. A significant increase in TNFα 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 polymethylmethacrylate membranes. A parallel increase in IL1β or IL6 mRNA was detected, and significant relationships were found between TNFα and IL1β (p < 0.001), and IL1β and IL6 gene expression (p < 0.05). Increased levels of mature TNFα and IL1β 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.

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          Assays for tumour necrosis factor and related cytokines

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            C5a stimulates secretion of tumor necrosis factor from human mononuclear cells in vitro. Comparison with secretion of interleukin 1 beta and interleukin 1 alpha

            We have demonstrated that purified C5a is a potent stimulus to human PBMC secretion of TNF-alpha, IL-1 beta, and IL-1 alpha, which proceeds in a dose-dependent fashion. At a given concentration of C5a, TNF-alpha and IL-1 beta secretion did not differ significantly; both were secreted in significantly greater quantity than IL-1 alpha. Clinical conditions such as Gram-positive and Gram-negative bacterial infections, trauma, and immune complex diseases activate complement. Through the mediation of TNF and IL-1 secreted in response to C5a, these diverse disorders can share common features of fever, coagulopathy, acute phase protein production, and disordered metabolism.
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              Interleukin 1 signal transduction


                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                February 1998
                12 February 1998
                : 16
                : 1
                : 30-36
                a Divisione Nefrologia e Dialisi, Modulo Fisiopatologia Clinica Nefrologica, Ospedale G. Bosco, b Dipartimento di Medicina ed Oncologia Sperimentale, Sezione di Patologia Generale, e c Istituto di Nefrologia, Università di Torino, Italia
                14310 Blood Purif 1998;16:30–36
                © 1998 S. Karger AG, Basel

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                Page count
                Figures: 2, References: 19, Pages: 7
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/14310
                Original Paper


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