PMID- 9690225
OWN - NLM
STAT- MEDLINE
DCOM- 19981015
LR  - 20220316
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 54
IP  - 2
DP  - 1998 Aug
TI  - Interleukin-6, interleukin-8 and monocyte chemotactic peptide-1 gene expression 
      and protein synthesis are independently modulated by hemodialysis membranes.
PG  - 570-9
AB  - BACKGROUND: Uremia produces a wide range of abnormalities of the immune system. 
      Blood-membrane interaction in hemodialysis results in activation and severe 
      dysfunction of peripheral blood mononuclear cells (PBMC). However, the question 
      of whether the use of different dialytic membranes may improve PBMC dysfunctions 
      remains unanswered. METHODS: To address this issue, the spontaneous interleukin 
      (IL)-6, IL-8 and monocyte chemotactic peptide-1 (MCP-1) gene expression and 
      protein release were studied in PBMC isolated from 7 healthy subjects, 8 uremic 
      patients on conservative therapy and 8 uremic patients undergoing subsequent one 
      month periods of hemodialysis with cuprophan (CU) and high-flux noncomplement 
      activating membranes, polymethylmethacrylate (PMMA) and polyamide (PA). At the 
      end of each period of treatment, PBMC were harvested at the beginning (T0) and 
      after 180 minutes of dialysis (T180), and then were cultured in complete medium. 
      IL-6, IL-8 and MCP-1 mRNA expression were studied by RT-PCR. In addition, MCP-1 
      gene expression was evaluated also by in situ hybridization. Cytokines released 
      in the supernatant were measured by ELISA. RESULTS: Compared to the control 
      group, PBMC from uremic patients on conservative therapy and treated by CU showed 
      a clear reduction in the cytokine release, while PMMA and PA membranes were able 
      to normalize IL-6, IL-8 and MCP-1 protein concentration, which had been reduced 
      by CU treatment. Interestingly, at T0, mRNA expression for all three cytokines 
      was increased in the patients treated by CU, when compared to the control group 
      and the uremic patients on conservative therapy. A further up-regulation was 
      observed at T180. PMMA and PA treatment, despite increasing the cytokine 
      secretion, significantly reduced the dialysis-induced cytokine gene expression. 
      CONCLUSION: PBMC exposure to CU membranes results in cytokine mRNA overexpression 
      associated with a paradoxically reduced protein release. In contrast, long-term 
      hemodialysis with synthetic high-flux membranes reduces IL-6, IL-8 and MCP-1 gene 
      expression and improves the ability of PBMC to secrete these cytokines. The 
      reduced cytokine secretion during bioincompatible dialysis may reflect a PBMC 
      adaptation that protects uremic patients against the inflammatory effects of 
      persistent cytokine release.
FAU - Pertosa, G
AU  - Pertosa G
AD  - Institute of Nephrology, University of Bari, Italy.
FAU - Grandaliano, G
AU  - Grandaliano G
FAU - Gesualdo, L
AU  - Gesualdo L
FAU - Ranieri, E
AU  - Ranieri E
FAU - Monno, R
AU  - Monno R
FAU - Schena, F P
AU  - Schena FP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Membranes, Artificial)
SB  - IM
MH  - Adult
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Female
MH  - Humans
MH  - Interleukin-6/*biosynthesis/genetics
MH  - Interleukin-8/*biosynthesis/genetics
MH  - Male
MH  - *Membranes, Artificial
MH  - Middle Aged
MH  - *Renal Dialysis
MH  - Transcription, Genetic
MH  - Uremia/*immunology
EDAT- 1998/08/05 00:00
MHDA- 1998/08/05 00:01
CRDT- 1998/08/05 00:00
PHST- 1998/08/05 00:00 [pubmed]
PHST- 1998/08/05 00:01 [medline]
PHST- 1998/08/05 00:00 [entrez]
AID - S0085-2538(15)30673-6 [pii]
AID - 10.1046/j.1523-1755.1998.00020.x [doi]
PST - ppublish
SO  - Kidney Int. 1998 Aug;54(2):570-9. doi: 10.1046/j.1523-1755.1998.00020.x.