Early elevation of plasma soluble CD14 subtype, a novel biomarker for sepsis, in a rabbit cecal ligation and puncture model
© BioMed Central Ltd 2008
Published: 13 March 2008
To reduce the mortality rates of patients with sepsis, rapid diagnosis and therapeutic decision are required. We have therefore discovered the soluble CD14 subtype (sCD14-ST), which is specific for sepsis and is elevated at an early stage during the disease progression . Additionally, we have been researching a novel fusion protein, MR1007, which consists of the modified light chain of interalpha inhibitor and the anti-CD14 antibody as an anti-sepsis agent.
We developed an ELISA using two rat monoclonal antibodies against N-terminal and C-terminal peptide sequences of rabbit sCD14-ST, respectively, to determine sCD14-ST concentrations in rabbit plasma. Survival rates and the time course of plasma levels of sCD14-ST, IL-6, and D-dimer were examined in a rabbit cecal ligation and puncture (CLP) model. Blood bacterial counts were also determined as colony-forming units.
The plasma sCD14-ST levels in seven dead animals clearly increased at 2 hours or later together with blood bacterial counts, reached the peak at 3 hours, and then gradually decreased at 4–8 hours, whereas those in one surviving animal did not. The induction phase was about 24 minutes and the half-life ranged from 4 to 5 hours. Additionally, the plasma IL-6 and D-dimer levels in dead animals clearly increased at 3 hours or later, whereas those in one surviving animal did not. Intravenous administration of MR1007 with an antibiotic, latamoxef sodium, following the observation of increases in sCD14-ST levels and blood bacterial counts, improved the survival and the plasma D-dimer levels in a rabbit CLP model (n = 9, P < 0.05).
Plasma sCD14-ST levels were elevated earlier than IL-6 and D-dimer along with occurrence of blood bacteria in a rabbit CLP model. Therapy with an anti-sepsis agent such as MR1007 following the elevation of sCD14-ST improved the outcome in the CLP model. These results suggest that sCD14-ST is useful to determine the earlier initiation of anti-sepsis therapy.