Primary Biliary Cirrhosis - cytokines, fatigue and quality of life

[Marco]

In the context of Julia Newton's ongoing comparative research on fatigue and autonomic dysfunction in PBC and ME/CFS (as discussed on the front page) the following recent study associates polymorphisms in TRAF1-C5 - a gene regulating the pro-inflammatory cytokine TNF-a with 'sickness behaviour' - fatigue, mental and physical function and mood.

TRAF1-C5 Affects Quality of Life in Patients with Primary Biliary Cirrhosis

http://www.hindawi.com/journals/cdi/2013/510547/

From the discussion (my breaks and bolds):

TRAF1-C5 plays an important role in the homeostasis of TNF-α, as well as a plethora of other cytokines with important pro-inflammatory actions [23, 35, 36].

Cholestatic disorders such as PBC are characterised by an imbalance of circulating pro-inflammatory and anti-inflammatory cytokines. This dysregulation may directly or indirectly influence sick behaviours, as the enhanced release of TNF-α within the brain contributes to the development of mood disorders and mental sickness [30–36].

In an animal model of cholestasis, Kerfoot et al. [31] have demonstrated in an increased infiltration of monocytes producing TNFα, which subsequently leads to further activation of resident brain macrophages able to produce TNFα.

Also, a fine Th1/Th2 immunity imbalance affects the IL-10/IL-12 regulatory circuit [14, 53, 54] and leads to over expression of IL-12 and TNF-α cytokines in patients with chronic fatigue. An increase of circulating TNF-α levels has been associated with significant fatigue in cholestatic patients with cancer [55]. Finally, work on animal models of chronic fatigue syndrome has also underlined the important pathogenic role of TRAF1-related cytokines, such as TNFα [32, 34]. These findings warrant further investigation.

 

[adreno]

Curcumin FTW.

 

[Enid]

Interesting Marco - for the simple reason my brother (Prof Neurology) is now diagnosed with liver autoimmunity, apart from everything else. What sets the immune system into autodrive.