In Vivo Studies of Serum C-reactive Protein Turnover in Rabbits

Abstract

A B S T R A C T We determined the plasma half-life of the acute phase protein C-reactive protein (CRP) both in normal rabbits and in rabbits that had received inflammatory stimuli. Rabbit CRP was purified from acute phase serum by Cx-polysaccharide affinity chromatography, radiolabeled, and rendered pyrogen-free. Six unstimulated rabbits were injected intravenously with '25I-CRP prepared by the lactoperoxidase method and four were injected with CRP labeled by methylation using ['4C]formaldehyde. Blood samples were obtained at 0.25 h and at intervals thereafter. Plasma half-life of CRP was calculated from the data generated during the first 12 h, by which time an average of 86% of labeled protein had disappeared from the blood stream. The mean half-life for CRP was 4.45±0.2 h, with no significant difference (0.40 < P < 0.45) between 125I-and '4C-labeled CRP. In six animals stimulated with either endotoxin or turpentine 24 h before injection of labeled CRP, a mean half-life of 5.8±0.6 h was found, not significantly different (0.30 <P <0.35) from unstimulated rabbits. We equated fractional catabolic rate to fractional disappearance rate, since the rate constant for passage of CRP from vascular to extravascular compartment can be assumed to be relatively small compared to the observed fractional disappearance rate. Fractional catabolic rate was independent of serum CRP concentration; average fractional catabolic rate in all 16 animals was 14±0.8% h-1 of the plasma pool. We were able to estimate rate of CRP synthesis, based on steady-state assumptions of pool sizes in those rabbits whose serum CRP levels did not change substantially during the period of study. Values as low as 6.7 ;tg/kg per h in

Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease.

“…The in vivo plasma clearance of 125I-CRP in mouse and rabbit was indistinguishable from that of isolated unlabeled CRP, or of CRP provided in whole acute phase serum. In mice the tl2 was 4 h and in the rabbit it was 7 h, values similar to those previously reported (31)(32)(33). Together with the precise mass spectrometric confirmation of the structure of the subunits of the single donor CRP and the in vitro biochemical evidence for full structural and ligand-binding integrity of the labeled CRP, these observations establish the validity of the present preparations as in vivo tracers of CRP metabolism.…”

“…Similarly, no differences were observed in patients with active SLE and polymyositis, in whom characteristically normal circulating levels of CRP were present. (31). CRP clearance was also unaffected by the intravascular presence of even macromolecular ligands to which CRP binds, such as apoB-containing lipoproteins (in the rabbit) or pneumococcal C-polysaccharide (32,33).…”

C‐Reactive protein: Current status and future perspectives

“…The maximum con-centrations were attained in 24-48 hr, and a rapid clearance from plasma occurred after the acute episode terminated. The half-life of CRP in rabbits given passively administered purified I2'I-labeled CxRP appeared to be around 6-7 hr (100,126). Human and mouse '251-labeled CRP given to mice demonstrated a T112 serum clearance of 4 hr (127).…”

Pilot study on serum C‐reactive protein in pet rabbits: clinical usefulness

“…In rabbits, the peak serum response occurs 38 hours after turpentine injection 1. The half‐life of serum CRP in both normal rabbits and rabbits that have received inflammatory stimuli is 4–6 hours 8. In an experimental study involving a rabbit mandibular bone infection model, the serum CRP level immediately increased and the peak level was reached within 3 days after inoculation 9.…”