Τομέας Παθολογίας
Library of the School of Health Sciences

2013-01-04

2012

Βασιλειάδη Δήμητρα -Αργυρώ

Ιωάννα Μαρία Δημοπούλου (επιβλέπουσα), Χαράλαμπος Ρούσσος, Μιχάλης Κουτσιλιέρης

Διερεύνηση της εξέλιξης των μεταβολικών διαταραχών στη σήψη και τη σηπτική καταπληξία

Greek

We have shown for the first time that adiponectin increases and resistin
decreases during the course of prolonged sepsis. These changes were most
evident in patients who recovered from the critical state and were assoaciated
with the reduction of the inflammatory response, as this was assessed by the
levels of proinflammatory cytokines. Adiponectin levels correlated with growth
hormone levels, suggesting a positive effect of growth hormone in adiponectin
secretion. Resistin levels mainly related to the severity of sepsis and the
degree of the inflammatory response suggesting that the main role of resistin
in humans is that of an acute phase protein.
We also characterized the changes of crucial stress hormones during prolonged
sepsis. Patients with the worst prognosis had significantly higher cortisol
levels, both basal and post ACTH stimulation, higher growth hormone levels and
lower DHEA-S levels. We also observed a gradual increase of ACTH and DHEA
concentrations in the course of sepsis; this finding has not been described
previously.
In conclusion, diverse endocrine and metabolic adaptations occur in critical
illness. Characterizing these changes opens the way for planning better
treatments for these patients, aiming at improving survival and accelerate
recovery. Towards this direction further studies are needed to delineate the
underlying pathophysiological mechanisms and to clarify which of these changes
are beneficial and which maladaptive in order to design clinical trials aiming
to modify those changes that are harmful. For example an early increase of
adiponectin and a reduction of resistin theoretically could have a beneficial
effect in reducing the inflammatory response and the marked insulin resistance.
However, the production of biosynthetic adiponectin for exogenous
administration has significant limitations as the molecule is subject to
several post-translational modifications. Furthermore it circulates at very
high plasma concentrations (5-30 mg /ml) and has a relatively short half-life
so that high amounts of recombinant protein and frequent administration would
be required. An alternative approach would be to increase endogenous
adiponectin. The administration PPAR-γ agonists has the advantage of increasing
the adiponectin and simultaneously reduce the levels of resistin. Existing
PPAR-γ agonists, thiazolidinediones, have several side effects such as fluid
retention resulting in peripheral edema and heart failure, and therefore they
are not suitable for use in ICU patients. Possibly newer more selective PPAR-γ
agonists may prove useful in the future.

Adiponectin, Resistin, ACTH, Cortisol, Growth hormne, Sepsis, Septic shock

No

0

Yes

357

xxiv, 123, III

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https://pergamos.lib.uoa.gr/uoa/dl/object/1306026