597 Chromogranin A and VS-1 in Plasma of Critically ill
Patients from Intensive Care Unit
In critically ill patients admitted to intensive care units (ICUs), severe diseases include
multiple organ failure with clinical and biochemical signs of systemic inflammation:
this corresponds to the systemic inflammatory response syndrome (SIRS) which is
typical of the early phase response to a stress of unspecified etiology. During this
response, major cardiovascular changes occur, and an activation of the adrenomedul-
lary response as well (Wortsman et al. 1984 ). The initial triggering factor in such
patients is frequently severe infection (Brun-Buisson 2000 ). Physicians have been
used to measure the time-dependent changes in plasma concentrations of C-reactive
protein and pro-calcitonin as sensitive and specific biomarkers to evaluate the level of
inflammation related to these pathophysiological conditions. However, both of these
parameters are unable to produce significant information as to outcome of such
patients (Harbarth et al. 2001 ). Therefore, clinicians are seeking for new biomarkers
that may reflect a link between initial SIRS, acute inflammation and outcome.
CGA is a marker of stress that exerts numerous autocrine, paracrine and endo-
crine functions (Taupenot et al. 2003 ); thus, it is capable of influencing the vascular
tone (Aardal and Helle 1992 ), the activity of the myocardium (Glattard et al. 2006 ),
and to reflect the level of activation of the sympathetic tone (Cryer et al. 1991 ).
Vasostatin-I (VS-I; CGA1–76), the highly conserved N-terminal fragment of CGA
(Figs. 3 and 4a), is predominantly produced and released in the circulation (Metz-
Boutigue et al. 1993 ; Aardal and Helle 1992 ). Its initial property was considered to
be its ability to relax contracted vessels (Aardal et al. 1993 ), but later it was shown
to stabilize heart functioning by counterbalancing the adrenergic-dependent stress
(Tota et al. 2007 ). The mechanistic actions of VS-I are still unclear in the absence of
classic receptors for this molecule, but it is involved in negative inotropism through
different biological pathways that could be integrated in a “whip- brake” conception
of cardiovascular homoeostasis (Tota et al. 2010 ). Furthermore, we have reported
that VS-1 is produced by PMNs and that it is involved in innate immunity by dis-
playing antimicrobial properties (Lugardon et al. 2000 ). In addition, CHR the active
sequence from VS-I activates PMNs (Zhang et al. 2009b).
In order to understand the role of CGA as a marker of stress during the time of
SIRS, in a first step we have analyzed the possibility of a correlation between CGA
concentrations, the inflammation biomarkers and the outcome in non-surgical criti-
cally ill patients with multiple organ failure (Zhang et al. 2008 , 2009a). In a second
step, we decided to evaluate the plasma VS-I levels in critically ill patients in order
to learn whether their changes would correlate with the severity of disease (defined
as death 28 days after admission) (Schneider et al. 2012 ).
Concerning the analysis of CGA in the plasma of critically ill patients, the popu-
lation consisted of 67 participants (Zhang et al. 2008 ) (53 participants and 14
healthy controls). In septic patients (n = 31), the infection focus was the respiratory
apparatus, the urinary or digestive tracts (n = 17, 8 and 6 respectively). On admission,
Involvement of Chromogranin A and Its Derived Peptides to Fight Infections