title: Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans.
abstract: BACKGROUND
  Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans.
  
  
  METHODS
  Thirteen male medical student volunteers (Caucasian, 21-30 years of age) were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing) plasma or (fibrinogen-free) serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes.
  
  
  RESULTS
  Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces.
  
  
  CONCLUSIONS
  In humans--as in rodents--biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior to, and shortly after, medical device implantation should improve the functionality and longevity of medical implants.
authors.affiliation: Department of Hand and Plastic Surgery, University Hospital, SE-581 85 Linköping, Sweden. johann.zdolsek@lio.se
authors.forename: Johann
authors.initials: J
authors.lastname: Zdolsek
authors.forename: John W
authors.initials: JW
authors.lastname: Eaton
authors.forename: Liping
authors.initials: L
authors.lastname: Tang
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000328:Adult; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D005340:Fibrinogen / Q000276:immunology*; D005549:Foreign-Body Reaction / Q000209:etiology* / Q000276:immunology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology; D011093:Polyethylene Terephthalates / Q000494:pharmacology; D019919:Prosthesis Implantation; D044967:Serum; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials; D006633:Histamine Antagonists; D011093:Polyethylene Terephthalates; D005340:Fibrinogen