Immune abnormalities in chronic fatigue sydrome associated with dysfunctional response to viruses

Researchers report that although no single viral cause for CFS has been found (e.g. Epstein-Barr), the type I interferon antiviral pathway has been repeatedly shown to be activated, particularly in those patients who are most disabled by their illness. The RNase L enzyme is a part of this immune system pathway and CFS patients have been found to have an abnormal form.

This antiviral pathway activation and abnormal RNase L has been noted by a number of different researchers and it has been suggested that it is this immune system activation that causes the main symptoms of CFS. This would seem to make sense if you think about how you feel when you have a viral infection such as the flu. It is not the virus itself that causes you to feel so weak and achey, it's your immune system's response to the infection. The levels of the abnormal RNase L have also been found to be associated with the severity of inflammatory symptoms.

The Belgian researchers however have gone further and report other associated abnormalities. They say that another enzyme, active double-stranded RNA-dependent kinase (PKR), is also elevated in CFS patients and corresponds to the antiviral pathway activation and presence of abnormal RNase L. They also report that the end result of the increase in PKR is an increase in levels of nitric oxide (NO).

Nitric oxide is used in various processes in the body, as a chemical messenger in the brain and in the regulation of blood pressure. It is a highly reactive molecule however, which led the Belgian researchers to conclude that the elevated levels of nitric oxide observed in CFS patients as the end result of the antiviral activation play an important role in the inflammation and disease process as a whole. The elevated NO would also result in a vicious cycle being set up in which the antiviral pathway is unable to shut down and return to the normal state, which in turn keeps NO levels elevated. This process could explain the chronic nature of CFS.

A number of doctors and independent CFS researchers, most notably Dr. Martin Pall, have suggested for a while now that NO plays a central role in CFS. This latest research helps to confirm their theories and provides another target for potential treatment.

Dr. Pall has developed a list of substances, mainly antioxidant nutrients, which should help to lower levels of NO and thus improve the health of CFS patients. Doctors specializing in CFS such as Dr. Paul Cheney have adopted this approach in some form or another and now use it with their patients.

Dr. Pall's NO theory of CFS along with his treatment suggestions and those of other CFS specialists can be found here.