Objectives: Procalcitonin (PCT) is a 13 kD protein of which plasma concentr
ations are strongly increased in inflammatory states, PCT concentrations ar
e claimed to have a more powerful discriminatory value for bacterial infect
ion than the acute phase proteins serum amyloid A (SAA) or C-reactive prote
in (CRP), The source of production and its mechanism of induction are unkno
wn, We investigated the inducibility of PCT both in vivo and in vitro and c
ompared the behavior of PCT with those of SAA and CRP,
Design: A prospective descriptive patient sample study and a controlled liv
er tissue culture study.
Setting: A university hospital,
Patients: Cancer patients who were treated with human tumor necrosis factor
-alpha (rhTNF-alpha; 5 patients) or interleukin-6 (rhIL-6; 7 patients),
Measurements and Main Results: Serial serum samples were collected for anal
ysis of concentrations of PCT, SAA, and GRP, In the TNF-alpha group, freque
nt sampling was performed on the first day to allow analysis of initial res
ponses, In a human liver slice model, the release of PCT, SAA, and CRP was
measured on induction with rhTNF-alpha and rhIL-6 for 24 hrs, We found that
PCT displayed acute phase reactant behavior in vivo after administration o
f both rhTNF-alpha and rhIL-6. after rhTNF-alpha-administration, PCT reache
d half-maximal concentrations within 8 hrs, 12 hrs earlier than either SAA
or GRP did. PCT, SAA, and CRP were produced in detectable quantities by liv
er tissue in vitro, PCT production by liver slices was enhanced after stimu
lation with rhTNF-alpha or rhIL-6; SAA and CRP concentrations were elevated
after stimulation with rhTNF-alpha.
Conclusions: We found that PCT and acute phase proteins such as CRP are ind
uced by similar pathways, The liver appears to be a major source of PCT pro
duction, Thus, PCT may be considered an acute phase protein. The different
kinetics of PCT, rather than a fundamentally different afferent pathway, ma
y explain its putative diagnostic potential to discriminate bacterial infec
tion from other causes of inflammation.