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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.