Tuesday, June 17, 2014

Immune Activity Different in Gulf War Illness and CFS


fulltext- https://www.landesbioscience.com/article/28948/full_text/#load/info/all

Systems Biomedicine • Volume 1 • Issue 3
Succumbing to the laws of attraction: Exploring the sometimes
pathogenic versatility of discrete immune logic
Paul Fritsch, Travis JA Craddock, Ryan M del Rosario, Mark A Rice,
AnneLiese Smylie, Virginia A Folcik, Gerda de Vries, Mary Ann
Fletcher, Nancy G Klimas, Gordon Broderick


Abstract
Feedback mechanisms throughout the immune and endocrine systems play a
significant role in maintaining physiological homeostasis.
Specifically, the hypothalamic-pituitary-adrenal (HPA) and
hypothalamic-pituitary-gonadal (HPG) axes contribute important
oversight of immune activity and homeostatic regulation. We propose
that these components form an overarching regulatory system capable of
supporting multiple homeostatic regimes. These emerge as a result of
the extensive feedback mechanisms involving cytokine and hormone
signaling. Here we explore the possible role of such alternate
regulatory programs in perpetuating chronic immune and endocrine
dysfunction in males. To do this we represent documented interactions
within and between components of the male HPA-HPG-immune system as a
set of discrete logic circuits. Analysis of these regulatory circuits
indicated that even in the absence of external perturbations this
model HPA-HPG-immune network supported three distinct and stable
homeostatic regimes. To investigate the relevance of these predicted
homeostatic regimes, we compared them to experimental data from male
subjects with Gulf War illness (GWI) and chronic fatigue syndrome
(CFS), two complex chronic conditions presenting with endocrine and
immune dysregulation. Results indicated that molecular profiles observed experimentally in male GWI and CFS were both distinct from the normal resting state. Profile alignments suggests that regulatory
circuitry is largely intact in male GWI and that the persistent immune
dysfunction in this illness may at least in part be facilitated by the
body's own homeostatic drive. Conversely the profile for male CFS was distant from all three stable states suggesting the continued influence of an exogenous agent or lasting changes to the regulatory circuitry such as epigenetic alterations.
 
 

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