title: Artificial surface-induced cytokine synthesis: effect of heparin coating and complement inhibition.
abstract: BACKGROUND
  Contact between blood and artificial surfaces induces an inflammatory response including activation of leukocytes and platelets, as well as complement and other plasma cascade systems. In the present study we investigated the roles of complement and surface modification in polyvinylchloride-induced cytokine production.
  
  
  METHODS
  Human whole blood was incubated in rotating loops of polyvinylchloride or heparin-coated polyvinylchloride tubing for 4 hours. Plasma concentrations of the cytokines tumor necrosis factor alpha, interleukin (IL) 1 beta, IL-6, IL-8, IL-10, and monocyte chemoattractant protein 1 (MCP-1) were quantified.
  
  
  RESULTS
  Polyvinylchloride induced a substantial increase in IL-8 and MCP-1, which was abolished by cycloheximide, indicating that they were synthesized during incubation. Interleukin 8 synthesis was completely complement-dependent since it was abolished by neutralizing antibodies to factor D and complement factor 5, as well as by a complement factor 5a receptor antagonist. Monocyte chemoattractant protein 1 synthesis was reduced by approximately half the amount by the complement inhibitors. Heparin-coated polyvinylchloride efficiently prevented synthesis of both IL-8 and MCP-1. Addition of recombinant human complement factor 5a to blood incubated in heparin-coated polyvinylchloride restored IL-8 and MCP-1 production completely and partly, respectively. In contrast to IL-8 and MCP-1, tumor necrosis factor alpha, IL-1 beta, interleukin 6 and IL-10 increased only marginally. A minor but significant increase in IL-1 beta was complement-dependent, whereas a similar increase in IL-10 was completely prevented by heparin-coated polyvinylchloride. No significant changes were observed for tumor necrosis factor alpha and IL-6.
  
  
  CONCLUSIONS
  Polyvinylchloride induced a marked increase in IL-8 and MCP-1, in contrast to a marginal increase in tumor necrosis factor alpha, IL-1 beta, IL-6, and IL-10. The increase in IL-8 and MCP-1 was prevented by heparin-coated polyvinylchloride. Interleukin 8 production was totally complement-dependent and mediated by complement factor 5a.
authors.affiliation: Department of Medicine, Nordland Hospital, Bodø, Norway. knut.lappegard@nlsh.no
authors.forename: Knut Tore
authors.initials: KT
authors.lastname: Lappegård
authors.forename: Michael
authors.initials: M
authors.lastname: Fung
authors.forename: Grethe
authors.initials: G
authors.lastname: Bergseth
authors.forename: Johan
authors.initials: J
authors.lastname: Riesenfeld
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001769:Blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000295:instrumentation; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000097:blood; D020099:Coated Materials, Biocompatible / Q000009:adverse effects; D003167:Complement Activation / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology; D003165:Complement System Proteins / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D016209:Interleukin-8 / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D011143:Polyvinyl Chloride / Q000009:adverse effects / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D000925:Anticoagulants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D020099:Coated Materials, Biocompatible; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015936:Complement C5a; D011143:Polyvinyl Chloride; D006493:Heparin; D003165:Complement System Proteins; D003513:Cycloheximide