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INTRODUCTION
Considerable progress in blood purification
techniques over the years has not
yet ended the ongoing discussion regarding
the exact place and most convenient
mode of blood purification in patients
with septic shock (1,2). Septic shock indeed
remains a leading cause of mortality
in intensive care patients (3), and sepsis
research focuses on developing
methods to improve outcome of this devastating
disease. Unfortunately, attempts
to decrease mortality in septic shock by
using pharmacological (4) and blood purification
(5,6) approaches have been disappointing.
Therefore, every effort to improve
the understanding of rationale of
blood purification can be seen as a key
process to succeed in therapy—an elegant
description is in the report by
Namas et al., published in this issue (7).
Despite growing insight into key
physiological aspects and valuable incentives
on technical issues, therapeutic
targeting and more adequate dose determination
(8), the rationale of blood purification
as part of treatment in severe
sepsis and septic shock is still questioned.
Sepsis is a complex and multifaceted
inflammatory condition (9) initiated
and rekindled by stimulated host immune
effector cells. The intensity of the
inflammation is determined by a myriad
of biologically active substances such as
cytokines, chemokines and reactive
oxygen/nitrogen species. This process
functions properly when mediators remain
restricted to specific tissues, inducing
a well-controlled inflammatory response
to local injury or infection.
However, any “overflow” of mediators
in the bloodstream may generate a relentless
and harmful systemic inflammation.
Sustained elevation and/or uncontrolled
production of pro- and
antiinflammatory cytokines may finally
turn into a toxic self-propagating cascade
reaction that causes remote organ
damage, multiorgan failure and, in some
patients, ultimately death (9).
THE “OLD” CYTOTOXIC APPROACH
For almost three decades, researchers
have invested in strategies that involved
removal of excess inflammatory media-
M O L M E D 1 8 : 1 3 6 3 - 1 3 6 5 , 2 0 1 2 | H O N O R E E T A L . | 1 3 6 3
Moving from a Cytotoxic to a Cytokinic Approach in the
Blood Purification Labyrinth: Have We Finally Found Ariadne’s
Thread?
Patrick M Honore,1 Rita Jacobs,1 Olivier Joannes-Boyau,2 Willem Boer,3 Elisabeth De Waele,1
Viola Van Gorp,1 Jouke De Regt,1 and Herbert D Spapen1
1Intensivist University Hospital, Vrije Universiteit Brussel (VUB), Brussels, Belgium; 2Haut Leveque University Hospital of Bordeaux,
University of Bordeaux 2, Pessac, France; and the 3Department of Anesthesiology and Critical Care Medicine, Hospital East Limburg,
Genk, Belgium
For almost three decades, researchers have invested in strategies that involved removal of excess inflammatory mediators from
the circulation (that is, the “cytotoxic” approach). Blood purification techniques using an extracorporeal device can indeed nonspecifically
remove a wide array of inflammatory mediators from the circulation. In animal models, this multimediator targeting or
pleiotropic approach was shown to downregulate systemic inflammation and to restore immune homeostasis. In this issue, Namas
et al. seriously challenge this cytotoxic hypothesis and propose to replace it by a cytokinic approach. In a rodent model of sepsis,
these authors elegantly demonstrate that hemoadsorption using a large surface-area polymer could reduce and, more importantly,
relocalize and reprogram sepsis-induced acute inflammation, while simultaneously lowering infectious burden and liver
damage. Although challenging, this new theory can be considered complementary to the existing cytotoxic hypotheses by coupling
reduced endothelial damage at the interstitial level (cytotoxic approach) with the concept of reprogramming leucocytes
and mediators toward infected tissue, thus emptying the bloodstream of important promoters of remote organ damages (cytokinic
approach).
Online address: http://www.molmed.org
doi: 10.2119/molmed.2012.00300
Address correspondence to Patrick Honore, ICU Department, University Hospital, Vrije
Universiteit, Brussels, 101, Laarbeeklaan, B-1090 Brussels, Belgium. Phone: [phone];
Fax: [phone]; E-mail: [e-mail].
Submitted June 7, 2012; Accepted for publication August 9, 2012; Epub
(www.molmed.org) ahead of print September 25, 2012.
tors from the circulation (that is, the “cytotoxic”
approach). Blood purification
techniques that an extracorporeal device
can indeed nonspecifically remove a
wide array of inflammatory mediators
from the circulation (10,11). In animal
models, this multimediator targeting or
pleiotropic approach was shown to
downregulate systemic inflammation
and to restore immune homeostasis (12).
In this issue, Namas et al. (7) seriously
challenge this cytotoxic hypothesis and
propose to replace it with a “cytokinic”
approach. They used the word cytokinic,
meaning that cytokines are attracting inflammatory
cells and in fact are messengers
between cells. Every technique that
can relocalize cytokines will also in itself
relocalize inflammation toward the infected
tissue and emptying secondary to
the blood compartment. In a rodent
model of sepsis, these authors elegantly
demonstrated that hemoadsorption
using a large surface-area polymer could
reduce and, more importantly, relocalize
and reprogram sepsis-induced acute inflammation
while simultaneously lowering
infectious burden and liver damage.

Read full study here:

https://molecularhub.org/forum/topics/default-category/37/37/cytokinic.pdf