Crit Care. 2008; 12(Suppl 2): P194.

Published online 2008 Mar 13. doi: 10.1186/cc6415

PMCID: PMC4088565

Early elevation of plasma soluble CD14 subtype, a novel biomarker for

sepsis, in a rabbit cecal ligation and puncture model
M Nakamura,1 T Takeuchi,1 K Naito,1 K Shirakawa,1 Y Hosaka,1 F Yamasaki,1 and S Furusako1
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Introduction
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 [1].
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.
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Methods
We developed an ELISA using two rat monoclonal antibodies against N-terminal and Cterminal 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.
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Results
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 48 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 IL6 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).
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Conclusion
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.
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References
1. Yaegashi Y, J Infect Chemother. 2005. pp. 234238. [PubMed] [Cross Ref]

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