Klimas/Vernon:

Cytokinenetwerken

stroken met

latente virale infektie(s)

 

 

 

 


 

Klimas en kollega's hebben de cytokinenetwerken bij ME/CVS-patiŽnten geanalyseerd.

Anders gesteld, ze hebben het "totaalpakket" bestudeerd i.p.v. de afzonderlijke cytokines.

 

 

 

 

Volgens de onderzoekers duiden de afwijkende cytokinenetwerken in ME/CVS op:

een verzwakte Th1 en Th17- en versterkte Th2-immuunresponse (Th1-Th2-shift) en

een verminderde reactie van NK-cellen op specifieke prikkels: cytokine IL-12 en LTα.

 

De klapper op de vuurpijl is de slotkonklusie van de auteurs:

de bevindingen stroken met processen die aktief zijn bij latente virale infektie.

 

 


 

A formal analysis of cytokine networks in chronic fatigue syndrome.

Brain, Behavior, and Immunity. 2010. doi:10.1016/j.bbi.2010.04.012.

Gordon Broderick, Jim Fuite, Andrea Kreitz, Suzanne D Vernon, Nancy Klimas, Mary Ann Fletcher.

 

 

Chronic Fatigue Syndrome (CFS) is a complex illness

affecting 4 million Americans

for which no characteristic lesion has been identified.

 

Instead of searching for

a deficiency in any single marker,

we propose that

CFS is associated with

a profound imbalance in the regulation of immune function

forcing a departure from standard preprogrammed responses.

 

To identify these imbalances

we apply network analysis to

the co-expression of 16 cytokines

in CFS subjects and healthy controls.

 

Concentrations of

IL-1a, 1b, 2, 4, 5, 6, 8, 10, 12, 13, 15, 17 and 23,

IFN-γ, lymphotoxin-α (LT-α) and TNF-α

were measured in the plasma of

40 female CFS and 59 case-matched controls.

 

Cytokine co-expression networks

were constructed

from the pair-wise mutual information (MI) patterns

found within each subject group.

 

These networks differed in topology

significantly more than expected by chance

with the CFS network

being more hub-like in design.

 

Analysis of local modularity isolated statistically distinct cytokine communities

recognizable as pre-programmed immune functional components.

 

These showed

highly attenuated Th1 and Th17 immune responses in CFS.

 

High Th2 marker expression

but weak interaction patterns

pointed to

an established Th2 inflammatory milieu.

 

Similarly,

altered associations in CFS provided

indirect evidence of diminished NK cell responsiveness to IL-12 and LTα stimulus.

 

These observations are

consistent with several processes active in latent viral infection

and would not have been uncovered by assessing marker expression alone.

 

Furthermore this analysis identifies

key sub-networks

such as IL-2: IFNγ: TNFα  

that might be targeted in restoring normal immune function.

 

 

 

Keywords:

cytokines; network theory; immune signaling; chronic fatigue; inflammation; latent viral infection

 

 

 

http://www.sciencedirect.com/

science?_ob=ArticleURL&_udi=B6WC1-500SJV5-1&_user=10&_coverDate=05%2F04%2F2010

&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221

&_version=1&_urlVersion=0&_userid=10&md5=9810357017be3bebef623c6bdde50c3b

 

 

 


 

Met dank aan Rob.