Mast cells and post-exertional malaise

By Paolo Maccallini

Background
There is a rare disease in which mast cells degranulation is induced by exercise of low intensity, particularly by exercises which require whole body involvement, such as jogging, aerobics and walking (Barg W et al. 2011). The name of this disease is exercise-induced anaphylaxis (EIA). There is another recently defined disorder due to abnormal activity of mast cells, the name of which is mast cell activation syndrome (MCAS), that has been linked to fatigue, brain fog, and orthostatic intolerance (Akin L, 2010).

The hypothesis
MCAS has been already somehow associated to ME/CFS by various Authors (Afrin L et al. 2016) however, to my knowledge, nobody has suggested that the possible link between CFS and MCAS may be an exercise induced increased release of mediators by mast cells. In other words post exertional malaise (PEM) could be -according to this hypothesis- a form of exercise-induced mast cell activation similar to EIA, but without anaphylaxis. A possible reason for exercise induced mediators release could be found in the abnormally high level of C4a, six hours after exercise in CFS (Sorensen, 2003). C4a -along with C4b- is the split product of C4, a protein of the complement system. As C4a is also an anaphylatoxin (i.e. a protein which stimulates mast cells) it could be a trigger for exercise induced activation. One of the feasible mechanisms for mast cells induced fatigue is the following one: release of fragmented mitochondria by activated mast cells (Zhang et al. 2012) may be a trigger for the cell danger response (CDR) through activation of the purinergic system, with consequent shut down of mitochondria (Naviaux R, 2013).

Experimental proof
This hypothesis can be verified measuring mast cells specific mediators after a physical effort. Those mediators are:

Less specific mast cells mediators are IL-1, IL-6, IL-8, TNF-alpha, and VEGF, among others.

Mast cells and Lyme disease
It has been demonstrated in vitro the potential for mast cells activation by B. burgdorferi spirochetes, with consequent TNF-α release (Talkington et al. 1999). Thus, a possible link between mast cells mediators and currently unexplained symptoms of Lyme disease and -more importantly- of post treatment Lyme disease syndrome (PTLDS), should be investigated.

Please, visit also this post on mast cells and anti-cardiolipin antibodies in CFS and Lyme disease.