title: IL-18 is involved in vascular injury in end-stage renal disease patients.
abstract: BACKGROUND
  The role of interleukin (IL)-6 and IL-18 in induction of the inflammatory reaction underlying arteriosclerosis, and protective effect of an anti-inflammatory cytokine IL-10 in this process, have been confirmed by experimental and clinical observations. A systemic inflammatory reaction marker, C-reactive protein (CRP), is known to be associated with the induction of IL-6 and IL-18 release. The chronic inflammatory state associated with renal insufficiency contributes to acceleration of arteriosclerosis, reflected by decreased elasticity which can be measured with aortal pulse wave velocity (PWV). It is well known that chronic kidney disease (CKD) is associated with the chronic inflammatory process, as evidenced by increase in CRP and IL-6 level. It also results in a drop of fetuin-A concentration which is the calcification inhibitor negatively regulated by inflammation. Part of the derangements associated with the progressive renal failure is also the rise of activated monocyte pool, which among others produces IL-18. The aim of the present study was to evaluate, through measurements of CRP, fetuin-A and aortal pulse wave velocity (aoPWV), whether IL-6 and IL-18 affect the arterial wall of CKD patients as a part of general inflammatory process or locally, through their effect on the arterial lesion development. Materials and methods. The study was performed in a group of 102 patients with stage V CKD (73 treated with haemodialysis and 29 treated with continuous ambulatory peritoneal dialysis) (CKD5 group) and in 30 healthy controls. We measured serum high-sensitivity C-reactive protein (hs-CRP), fetuin-A, IL-6, IL-18, IL-10 (ELISA) and others (haemoglobin level, white blood cell count, serum calcium, phosphate, calcium-phosphate product, albumin, fibrinogen, cholesterol, high-density lipoprotein (HDL), triglycerides and parathormone). ECG-gated carotid and femoral artery waveforms were recorded and analysed.
  
  
  RESULTS
  Serum levels of hs-CRP, IL-6, IL-10 and IL-18 were higher and fetuin-A levels were lower in the CKD5 group than in controls [6.4 (0.6-22.3) mg/dl versus 2.5 (0.5-5.2) mg/dl; 8.29 pg/ml (0.96-74.48)] versus 2.78 (7.91-0.77) pg/ml; 6.5 (3.7-29.7) pg/ml versus 4.1 (3.8-7.2) pg/ml; 254.4 (468.8-47.5) pg/ml versus 89.3 (91.3-27.5) pg/ml]. The aoPWV was higher in the CKD5 group patients than in the control group (9.4 +/- 1.75 m/s versus 7.76 +/- 1.67 m/s; P < 0.05, respectively). Serum fetuin-A level was negatively associated with hs-CRP and IL-6 but not with IL-18 or IL-10. The aoPWV positively correlated with hs-CRP (r = 0.246; P < 0.05), IL-6 and IL-18 (r = 0.220; P < 0.05) and negatively correlated with fetuin-A (r = -0.204; P < 0.05). No relationship between IL-10 and aoPWV was found. In a multiple regression analysis model respecting inflammatory markers the influence of hs-CRP, IL-18 and fetuin-A on aoPWV remained significant.
  
  
  CONCLUSIONS
  The novel observations in the present study are the data indicating that the distinctive contribution of IL-18, but not IL-6, to the arteriosclerosis occurrence in CKD patients, is independent from CRP, fetuin A or other factors involved in the general inflammatory process.
authors.affiliation: Department of Nephrology and Transplantation Medicine, Wrocław Medical University, ul. Traugutta 57/59, 50-417 Wrocław, Poland. porazko@gazeta.pl
authors.forename: Tomasz
authors.initials: T
authors.lastname: Porazko
authors.forename: Jakub
authors.initials: J
authors.lastname: Kúzniar
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kusztal
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Kúzniar
authors.forename: Wacław
authors.initials: W
authors.lastname: Weyde
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kuriata-Kordek
authors.forename: Marian
authors.initials: M
authors.lastname: Klinger
mesh_terms: D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D001798:Blood Proteins / Q000378:metabolism; D001808:Blood Vessels / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D004548:Elasticity; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D020382:Interleukin-18 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D006435:Renal Dialysis; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D001798:Blood Proteins; C508600:IL6 protein, human; D018836:Inflammation Mediators; D020382:Interleukin-18; D015850:Interleukin-6; D060749:alpha-2-HS-Glycoprotein; D002097:C-Reactive Protein