title: Paricalcitol effects on activities and metabolism of platelet activating factor and on inflammatory cytokines in hemodialysis patients.
abstract: OBJECTIVE
  Paricalcitol improves the inflammatory status of hemodialysis patients. PAF is a strong inflammatory mediator which is produced during hemodialysis. We studied the effects of paricalcitol on PAF and other inflammatory mediators implicated in chronic kidney disease (CKD).
  
  
  METHODS
  We examined the in vitro effects of paricalcitol on PAF/thrombin-induced aggregation as well as on the activities of PAF-basic metabolic enzymes, lyso-PAF acetyltransferase (Lyso-PAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol cholinephospho-transferase (PAF-CPT) and PAF-acetylhydrolase (PAF-AH) in blood cells from healthy volunteers. In addition, the in vivo effects of paricalcitol on the above these enzymes were examined in plasma and blood cells of hemodialysis patients who had not received any type of vitamin D treatment during the last three months before and after receiving paricalcitol for a month. Finally, IL-12p70, IL-1β, IL-6, IL-8 and TNF-α were measured.
  
  
  RESULTS
  Paricalcitol inhibited in vitro PAF/thrombin-induced platelet aggregation and the inhibitory effect was comparable with that of PAF/thrombin antagonists. In addition, paricalcitol inhibited in vitro PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while much higher concentrations of paricalcitol were needed to inhibit Lyso-PAF-AT activity. Similarly, in hemodialysis patients, paricalcitol treatment reduced PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while it could not influence Lyso-PAF-AT activity. On the other hand, paricalcitol therapy reduced IL-8, IL-1β, and TNF-α.
  
  
  CONCLUSIONS
  These results further support the beneficial effects of vitamin D treatment in hemodialysis patients, since it strongly affects PAF/thrombin activities, PAF-metabolism, and IL-8, IL-1β and TNF-α circulating levels.
authors: Faculty of Chemistry, National & Kapodistrian University of Athens, Panepistimioupolis, Athens - Greece. sofiaverouti@yahoo.gr
authors: Sophia N
authors: SN
authors: Verouti
authors: Alexandros B
authors: AB
authors: Tsoupras
authors: Fotini
authors: F
authors: Alevizopoulou
authors: Constantinos A
authors: CA
authors: Demopoulos
authors: Christos
authors: C
authors: Iatrou
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D000123:Acetyltransferases / Q000097:blood; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D002798:Diacylglycerol Cholinephosphotransferase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D010865:Pilot Projects; D010972:Platelet Activating Factor / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
chemical_list: D016207:Cytokines; D004872:Ergocalciferols; D018836:Inflammation Mediators; D010972:Platelet Activating Factor; C084656:paricalcitol; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D002798:Diacylglycerol Cholinephosphotransferase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D013917:Thrombin