Pro- and anti-inflammatory cytokines in chronic pediatric dialysis patients: effect of aspirin.
Dialysis provides effective and safe treatment of ESRD in children, but patients who are maintained on chronic dialysis are at risk for cardiovascular disease. One major risk factor for cardiovascular disease in adult patients with ESRD is chronic inflammation. The effect of anti-inflammatory therapy with aspirin on serum cytokine concentration was studied in seven children who were receiving hemodialysis (HD) and seven who were receiving continuous cycling peritoneal dialysis (CCPD or PD). Dialysis vintage was 4.3 +/- 4.6 yr; single-pool Kt/V was 1.46 +/- 1.4, mean equilibrated Kt/V was 1.27 +/- 0.16, and PD weekly Kt/V was 2.45 +/- 0.30. Baseline proinflammatory cytokine IL-1beta, IL-6, IL-8, and TNF-alpha serum concentrations were significantly elevated, whereas serum anti-inflammatory cytokine IL-4 and IL-10 concentrations were normal. The patterns of cytokine elevation were similar for patients who were receiving HD versus PD. IL-4 and IL-6 concentrations demonstrated strong positive correlation with dialysis vintage (IL-4, P < 0.03; IL-6, P < 0.0001). Pre-aspirin serum cytokine concentrations did not vary with single-pool Kt/V or equilibrated Kt/V for HD patients or with weekly Kt/V for PD patients. Serum IL-8 and TNF-alpha concentrations were significantly reduced by aspirin treatment at 4 mo (P = 0.04 and P = 0.007, respectively). Serum IL-6 concentration decreased with aspirin treatment but not significantly (P = 0.1). Serum IL-1beta concentration remained unchanged, and IL-4 and IL-10 concentrations remained stable throughout aspirin treatment. The effect of aspirin treatment on serum cytokine concentrations was similar for HD and PD patients. In HD patients, IL-6, IL-8, and TNF-alpha remained suppressed 1 mo after discontinuation of aspirin. It is concluded that proinflammatory cytokines are elevated in pediatric HD and PD patients without counterbalance from anti-inflammatory cytokines, and aspirin therapy attenuates inflammation.
Goldstein
Stuart L
SL
Department of Pediatrics, Renal Section, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.
Leung
Jocelyn C
JC
Silverstein
Douglas M
DM
D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D002648:Child; D016207:Cytokines / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D010446:Peptide Fragments / Q000097:blood; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010865:Pilot Projects; D006435:Renal Dialysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; C508609:IL10 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C052994:interleukin-1beta (163-171); D016753:Interleukin-10; D015847:Interleukin-4; D001241:Aspirin