title: Infusion of pharmaceutical-grade natural human C-reactive protein is not proinflammatory in healthy adult human volunteers.
abstract: BACKGROUND
  Baseline circulating concentrations of C-reactive protein (CRP) are significantly associated with cardiovascular disease risk in general populations. This modest association has been inappropriately conflated with causality, and it has been claimed that CRP is proatherogenic. Most of the known causative factors for atherosclerosis stimulate increased CRP production, but comprehensive genetic epidemiology studies provide no support for a pathogenic role of CRP. The reported proinflammatory effects of human CRP preparations on healthy cells in vitro and in healthy animals in vivo have all been produced by poorly characterized CRP preparations, demonstrably caused by impurities, or elicited by CRP made in recombinant Escherichia coli not by humans. None of the in vitro or animal findings have been reproduced with pure natural human CRP. Nevertheless, the strong proinflammatory effects of infusing recombinant bacterial CRP into humans have still been inappropriately ascribed to CRP.
  
  
  OBJECTIVE
  To investigate the effects of infusion into healthy adult human volunteers of pure natural human CRP.
  
  
  RESULTS
  Comprehensively characterized, pharmaceutical-grade, endotoxin-free, purified CRP, prepared to GMP standard from pooled normal human donor plasma was infused as an intravenous bolus in 7 healthy adult human volunteers at ≤2 mg/kg to provide circulating CRP concentrations ≤44 mg/L. No recipient showed any significant clinical, hematologic, coagulation, or biochemical changes, or any increase in proinflammatory cytokines or acute phase proteins.
  
  
  CONCLUSIONS
  The human CRP molecule itself is not proinflammatory in healthy human adults.
authors: From the Wolfson Drug Discovery Unit, and the National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College London, London, United Kingdom (M.B.P., T.L., H.J.L., J.D.G., P.N.H.); Department of Clinical Biochemistry, Royal Free Hospital, London, United Kingdom (N.W.); and the National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom (S.P., Y.M.).
authors: Thirusha
authors: T
authors: Lane
authors: Nancy
authors: N
authors: Wassef
authors: Stephen
authors: S
authors: Poole
authors: Yogesh
authors: Y
authors: Mistry
authors: Helen J
authors: HJ
authors: Lachmann
authors: Julian D
authors: JD
authors: Gillmore
authors: Philip N
authors: PN
authors: Hawkins
authors: Mark B
authors: MB
authors: Pepys
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology; D002097:C-Reactive Protein / Q000008:administration & dosage* / Q000276:immunology / Q000302:isolation & purification; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D007262:Infusions, Intravenous; D008297:Male; D000685:Serum Amyloid A Protein / Q000378:metabolism; D055815:Young Adult
chemical_list: D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein
keywords: C-reactive protein; cardiovascular physiological phenomena; healthy volunteers; inflammation