Korean Journal of Nephrology 1993;12(4):633-648.

장기 혈액투석 환자의 혈장 IL - 1 , TNFa , IL - 6 농도 및 말초혈액 단핵세포에서의 생산능

안재형 , 박재경 , 이태원 , 임천규 , 김명재 , 김영훈

Abstract

To evaluate the role of the cytokines in the inflamma- tory responses induced by blood interaction with hemodialysis membranes and the effect of recombinant human erythropoietin (rHuEPO) an cytokine production, I have investigated the plasma IL-1, TNFa, IL-6 concentrations and the productions by 24-hours cultured peripheral blood mononuclear cells (PBMC) isolated from: (a) 8 healthy control subjects (Group 1)(b) 7 patients with end-stage renal disease without dialysis (Group 2)(C) 9 hemodialyzed patients without rHuEPO (Group 3)(d) 9 hemodialyzed patients with rHuEPO (Group 4). And to evaluate the effect of the native properties of membranes, I have investigated the pre- and post-dialysis plasma concentrations of IL-1, TNFa, IL-6 and the productions by 24-hours cultured PBMC in group 4, who have used PMMA membrane over 6 months, using the following criteria: (1) in last dialysis with PMMA membranes (PMMA1)(2) in 6" times of dialysis with cuprophan membranes (3) in further 6'" times of dialysis with PMMA membranes (PMMA2). The results were as follows: 1) The plasma IL-1 concentrations of pre-PMMA1 in group 3(42. 05±1 93 fmol/ml) and group 4(45 32±2 63 fmol/ml) were significantly high compared to that in group 1(33 81±2 38 fmol/ml)(each p<0 05). 2) The plasma TNFa concentrations of pre-PMMA1 in group 2(12. 44±1. 56 fmol/ml), group 3(12 01±1 29 fmol/ml), group 4(8 .89±0. 51 fmol/ml) were significant- ly low compared to that in group 1(29. 54±1.99 fmol/ ml)(each p<0 05). 3) The TNFa productions by 24-hours cultured PBMC in group 2(33. 05±10, 59 fmol/ml) was signific- natly low compared to that in group 1(72. 40±11. 70 fmol/ml)(p<0 05). 4) The plasma IL-1 concentrations were significantly decreased after dialysis in using Cuprophan (43.74±3. 57 vs. 31. 40±3. 60 fmol/ml: p<0 001) and PMMA2 (40. 21±3.16 vs. 35. 44±2.38 fmol/ml:p<0 05) membranes in group 4. 5) The plasma IL-1 concentration in pre-PMMA2 (40, 21±3 .16 fmol/ml) was significantly low compared to those in pre-PMMA1(45. 32±2. 63 fmol/ml:p<0 01) and pre-Cuprophan (43. 74±3. 57 fmol/ml:p<0.05) in group 4. 6) The IL-1 productions by 24-hours cultured periph- eral blood mononuclear cells (PBMC) in pre-Cuprophan (29.77±6,18fmol/ml) and pre-PMMA2(25 .36±3,53 fmol/ml) were significantly low compared to that in pre-PMMA1(46.88±7.33 fmol/ml) in group 4 (each p< 0 05). 7) The IL-6 productions by 24-hours cultured PBMC in pre-PMMA2(264.8±60.8 fmol/ml) was significantly low compared to pre-PMMA1(604.0+78.5 fmol/ml)(p< 0.05). 8) There were significant correlations between IL-1 and TNFu(r=0.59, p<0 001), IL-1 and IL-6(r=0 69, p<0.001), TNFa and IL-6(r=0.59, p<0 001) in the productions by 24-hours PBMC. These data suggest that IL-1, TNFa, IL-6 are produced interrelatedly by PBMC and IL-1 are more correlated with the inflammatory responses induced by blood interaction with hemodialysis membrane than TNFa or IL-6 in chronic hemodialyzed patients. The effect of rHuEPO on cytokine production is minimal and the productions of these cytokines by PBMC may be induced by long-term, not short-term, stimulations with hemodialysis membranes without regard to membrane types.