Innate Immune Changes in the Peripheral Blood of Chronic Fatigue Syndrome Patients: Risk Factors for Disease Progression and Management (pp. 91-130)
Authors: (Deborah L.S Goetz, Judy A. Mikovits, Jamie Deckoff-Jones, Francis W. Ruscetti, LANDRES Management Consultant, MAR Consulting Inc., Private CFS Practice, and others)
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 antiinflammatories,
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.
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