title: The artificial surface-induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent.
abstract: Exposing blood to an artificial surface results in a systemic inflammatory response, including cytokine release and complement activation. We studied the artificial surface-induced inflammation in human whole blood using an extensive panel of inflammatory mediators including proinflammatory cytokines, chemokines and growth-factors and investigated the role of the complement system in the induction of this response. Using multiplex technology, 27 different inflammatory mediators were measured after circulating blood for 4 hours in polyvinyl chloride tubing. The C3 inhibitor compstatin was used to block complement activation. A significant (p < 0.05) increase in 14 of the 27 mediators was induced by the surface, of which 7 were chemokines (IL-8, MCP-1, MIP-1alpha, MIP-1beta, RANTES, eotaxin and IP-10) and 5 were growth-factors (G-CSF, GM-CSF, VEGF, PDGF and FGF). The traditional proinflammatory cytokines like IL-1beta, TNFalpha and IL-6 were not induced, although IL-6, as well as IL-15 and IL-17 increased if the surface was coated with highly bioincompatible laminaran. Inhibition of complement activation with compstatin significantly (p < 0.05) reduced the formation of 12 of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or more, for the remaining two the inhibition was more moderate. A highly biocompatible heparin-coated PVC surface was used as negative control and completely abolished the whole inflammatory response. The artificial surface PVC markedly induced a broad spectrum of chemokines and growth-factors, which was largely dependent on activation of complement.
authors: Department of Medicine, Nordland Hospital, Bodø, Norway. knut.lappegard@nlsh.no
authors: K T
authors: KT
authors: Lappegård
authors: G
authors: G
authors: Bergseth
authors: J
authors: J
authors: Riesenfeld
authors: A
authors: A
authors: Pharo
authors: P
authors: P
authors: Magotti
authors: J D
authors: JD
authors: Lambris
authors: T E
authors: TE
authors: Mollnes
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D018925:Chemokines / Q000097:blood / Q000187:drug effects*; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000187:drug effects*; D005936:Glucans; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology; D011143:Polyvinyl Chloride / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D018925:Chemokines; D003176:Complement C3; D016207:Cytokines; D005936:Glucans; D010456:Peptides, Cyclic; D011134:Polysaccharides; C111828:compstatin; D011143:Polyvinyl Chloride; D006493:Heparin; C008247:laminaran