Book chapter abstract:
Chronic Fatigue Syndrome (CFS) is recognized by the WHO as an alternative name for Myalgic Encephalomyelitis, which has been classified as a disease of the central nervous system since 1969.
The concept that chronic microbial infection drives constant activation of the innate immune system through alterations in the production of innate immune cells and accompanied by abnormal production of pro-inflammatory cytokines and chemokines, and that this leads to progressive immune deficiency seen in many CFS patients has only recently been appreciated.
In investigating the distribution of immune cells in the peripheral blood of a cohort of CFS patients who have an antibody recognizing the SFFV envelope protein, we discovered profound alterations in the number and types of cells, particularly in the cells regulating the innate immune system. These changes included chronic activation of monocytes and dendritic cells, and a marked increase in NKT cells and decrease in NK cells.
The cytokines in plasma from these CFS patients was assayed in a multiplex platform, and one of us published findings showing signatures of infection; that is, significantly high levels of many proinflammatory mediators such as IL-12, MCP-1, IL-8, IP-10, IL-6, TNF-α, and IL-1β while being low in the critical antiviral cytokine IFN-α. In expanding these results, we found that subsets of these CFS patients had increased TGF-β and others had increased
IL-9.
We will discuss these and other published results that suggest that chronic
stimulation of the innate immune system is a component of the development and progression of disease in many CFS patients. In chronic diseases the resulting immunodeficiency allows activation and replication of many secondary pathogens. Thus CFS patients can share complex pathogenic complications with patients with HIV AIDS and HTLV-1 associated myelopathy.
In many CFS patient populations, the presence of several concomitant infections, from Borrelia burgdorferi to reactivated exogenous and endogenous viruses, chronically dysregulating the immune system, is a major risk factor in the development of pathology. Other risk factors include alterations in microbiota regulation, mitochondrial toxicity, cognitive dysfunction and impaired methylation pathways. These factors can also increase the risk of others diseases, including cancer, in some CFS patients.
These results have important implications for the management of many people with this diagnosis. We will review in this chapter the use of anti inflammatories, anti-virals and other therapies, as well as discussing how repurposing drugs holds promise in the treatment of patients displaying the immune abnormalities identified in these CFS patients.
Innate Immune Changes in the Peripheral Blood of Chronic Fatigue Syndrome Patients: Risk Factors for Disease Progression and Management, by Deborah L.S Goetz, Judy A. Mikovits, Jamie Deckoff-Jones, Francis W. Ruscetti. Chapter 6 in Chronic Fatigue Syndrome, edited by Connor Hudson, pp. 91-130.
