Chronic Immune Response Hypothesis for Chronic Fatigue Syndrome: Experimental Results and Literature Overview

Abstract

Chronic fatigue is characterized by severe disabling fatigue associated with physical, mental, and immunological disturbances. Chronic fatigue lasting for more than 6 months is known as chronic fatigue syndrome (CFS). This condition has been known for at least two centuries under the names “neurasthenia”, “post-viral fatigue”, “myalgic encephalomyelitis” or “chronic mononucleosis”. The estimated worldwide prevalence of CFS is about 1% and this number can be under estimated due to mild character of the symptoms which can be explained by normal reasons. No physical examination signs are specific to CFS; no diagnostic tests identify this syndrome; no definitive treatment for it exists. Pathophysiology of CFS is analyzed from various points of view among which a relation to chronic infections or/and hypothalamic-pituitary adrenal (HPA) axis disturbances seem to be the most important ones. Up to now there are no convincing evidences found to support any of the proposed hypothesis trying to explain its pathogenesis. The current concept is that chronic fatigue condition is multi-factorial where an unidentified infective agent causes an aberrant ongoing immune response which fails to be switched-off [Lorusso L et al, 2009]. Here we put forward a new hypothesis that this “unidentified” infective agent is mycobacteria, and protective response controlling mycobacterial infection exhausts immunity and total reserves of body leading to chronic fatigue [Roth J et al, 2011]. CFS is a long-lasting condition. Among 265 patients with established CFS diagnosis studied by Tirelli U et al. [1994] many patients reported profound fatigue, lasting from 6 months to 10 years, among them 102 (38%) patients had to stop their working activities for a period of time ranging from 3 months to 2 years. CFS affects all racial-ethnic groups and more often females than males [Dinos S et al, 2009]. The prevalence of women is estimated from 6 to 1 [Capelli E et al, 2010] to no difference [Ravindran MK et al, 2011]. CFS is rarely found in childhood and adolescence however often affects young adults from 20 to 40 years old. The diagnosis of CFS is based on clinical criteria and depends on exclusion of other physical and psychiatric diseases. Besides significant, unexplained fatigue lasting more than 6 months, at least 4 of 8-11 additional symptoms should be present: 4-5 of immunological nature such as sore throat or lymph nodes; joint or muscle pain; irritable bowel syndrome; and 4-6 neurological ones: headaches, problems with concentration or memory; dizziness, impaired co-ordination, sleep disturbances; post-exertional exhaustion [Sharpe MC et al, 1991].