Infusion of Pharmaceutical Grade Natural Human C Reactive Protein is not Pro Inflammatory in Healthy Adult Human Volunteers
Rationale: 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 pro atherogenic. 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 pro inflammatory 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, or demonstrably caused by impurities, or elicited by CRP made in recombinant E. coli not by humans. None of the in vitro or animal findings have been reproduced with pure natural human CRP. Nevertheless the strongly pro inflammatory 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.
Methods and 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 up to 2 mg/kg to provide circulating CRP concentrations up to 44 mg/L. No recipient showed any significant clinical, hematological, coagulation or biochemical changes, nor any increase in pro inflammatory cytokines or acute phase proteins.
Conclusions: The human CRP molecule itself is not pro inflammatory in healthy human adults.
- Received October 7, 2013.
- Revision received December 5, 2013.
- Accepted December 11, 2013.