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A role for homeostatic drive in the perpetuation of complex chronic illness

Discussion in 'Latest ME/CFS Research' started by Ecoclimber, Jan 16, 2014.

  1. Ecoclimber

    Ecoclimber Senior Member

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    PLoS One. 2014 Jan 8;9(1):e84839. doi: 10.1371/journal.pone.0084839.
    A role for homeostatic drive in the perpetuation of complex chronic illness: gulf war illness and chronic fatigue syndrome.
    Craddock TJ1, Fritsch P2, Rice MA Jr3, Del Rosario RM3, Miller DB4, Fletcher MA5, Klimas NG6, Broderick G7.
    Author information

    Abstract

    A key component in the body's stress response, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates changes across a broad range of major biological systems.

    Its dysfunction has been associated with numerous chronic diseases including Gulf War Illness (GWI) and chronic fatigue syndrome (CFS).

    Though tightly coupled with other components of endocrine and immune function, few models of HPA function account for these interactions. Here we extend conventional models of HPA function by including feed-forward and feedback interaction with sex hormone regulation and immune response. We use this multi-axis model to explore the role of homeostatic regulation in perpetuating chronic conditions, specifically GWI and CFS.

    An important obstacle in building these models across regulatory systems remains the scarcity of detailed human in vivo kinetic data as its collection can present significant health risks to subjects.

    We circumvented this using a discrete logic representation based solely on literature of physiological and biochemical connectivity to provide a qualitative description of system behavior. This connectivity model linked molecular variables across the HPA axis, hypothalamic-pituitary-gonadal (HPG) axis in men and women, as well as a simple immune network. Inclusion of these interactions produced multiple alternate homeostatic states and sexually dimorphic responses.

    Experimental data for endocrine-immune markers measured in male GWI subjects showed the greatest alignment with predictions of a naturally occurring alternate steady state presenting with hypercortisolism, low testosterone and a shift towards a Th1 immune response.

    In female CFS subjects, expression of these markers aligned with an alternate homeostatic state displaying hypocortisolism, high estradiol, and a shift towards an anti-inflammatory Th2 activation.

    These results support a role for homeostatic drive in perpetuating dysfunctional cortisol levels through persistent interaction with the immune system and HPG axis.

    Though coarse, these models may nonetheless support the design of robust treatments that might exploit these regulatory regimes.
     
    Last edited: Jan 16, 2014
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  2. Snow Leopard

    Snow Leopard Senior Member

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    Its an interesting attempt. All models like this fall well short of describing real systems, but I think such modelling could be useful in a serious research programme. Unfortunately no one is funding such a programme (basically measure stuff, build model, use model to make predictions on stuff to measure, revise, etc).

    Of note, this model explicitly denies the possibility of male CFS being caused by a hypocortisol state:

    One of the main criticisms I have with this paper and the previous models by these authors is that they fail to explain the real dynamic range of real expression of GR, cortisol. Eg the recent Light et al study which found GR expression to be normal at rest, but abnormal in patients after repeat exercise.
     
  3. Snow Leopard

    Snow Leopard Senior Member

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    The conclusion is nice:

    That seems to be an alien concept for the treatments of chronic illnesses today!
     
    rosie26 and Ecoclimber like this.
  4. Ecoclimber

    Ecoclimber Senior Member

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