Chronic Fatigue Syndrome and IL-10
A new 2015 study, published in the Mediators of Inflammation journal suggests a deficiency of interleukin (IL)-10 in chronic fatigue syndrome (CFS).
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), an illness characterized by unexplained fatigue lasting 6 months or more, is often linked to dysfunctional neuroendocrine and immune responses, including abnormal production of several cytokines (NG Klimas & A O’Brien Koneru, 2007).
The term Chronic Fatigue Syndrome (CFS) was introduced in 1988 but an umbrella term – neuroendocrine-immune dysfunction syndrome (CNDS) is also often used (LA Jason et al., 2003).
Immunological dysregulation has been proposed as a significant component of Chronic Fatigue Syndrome. Reductions in natural killer (NK) cytotoxic activity and elevations in regulatory T cells (Tregs) are the most consistent findings associated with Chronic Fatigue Syndrome.
While cytokines have been investigated in CFS/ME patients, the cyclical nature of cytokine secretion makes it difficult to determine the specific cytokine(s) implicated in the pathomechanism of Chronic Fatigue Syndrome. Additionally, the results are frequently inconsistent; for example, elevations in interleukin- (IL-) 8 and decreases in IL-8 have both been reported. In CFS/ME, cytokines such as IL-4, IL-10, IL-17, tumor necrosis factor- (TNF-) α, and interferon– (IFN-) γ have been observed to be equivocally expressed in the serum and plasma samples and following mitogenic or inflammatory stimulation of lymphocytes.
The ‘immune hormone’ IL-10 is a major anti-inflammatory cytokine in periphery and the central nervous system (CNS). IL-10 downregulates the pro-inflammatory immune responses related to the T helper (Th1) cell axis, and, in general, the production of most of the pro-inflammatory cytokines. This includes a suppression of cytokine production and the expression of cytokine receptors in brain’s microglia cells (M Sawada et al., 1999).
In the Mediators of Inflammation study, D. Peterson and colleagues from the Simmaron Research, NV, USA and the Griffith University, Parklands, Australia collected cerebrospinal fluid (CSF) samples from Chronic Fatigue Syndrome patients at the time of diagnosis.
The study comprised 18 CFS/ME patients and 5 healthy controls. CFS/ME patients were defined using the 1994 Centre for Disease Prevention and Control Criteria (1994 CDC) for CFS/ME. CSF samples were collected from patients in the USA at the time of diagnosis via lumbar puncture.
IL-1β, IL-1ra, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17, basic FGF, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), IFN-γ, interferon gamma-induced protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein 1 (MIP-1)α, MIP-1β, platelet-derived growth factor- (PDGF-) BB, regulated on activation, normal T cell expressed and secreted (RANTES), TNF-α, and vascular endothelial growth factor (VEGF), were simultaneously examined in all CSF samples from all participants via the Bio-Plex Pro Human Cytokine 27-plex Assay (Bio-Rad).
The authors report that of the 27 cytokines examined; only IL-10 was significantly decreased in the CFS group, as compared to healthy control individuals.
A reduction in IL-10 may increase inflammation in the CNS as it may suggest increases in c-Jun N-terminal kinase (JNK) which is a known inducer of helper T cell differentiation and secretion of proinflammatory cytokines. As hippocampal related IL-10 is known to suppress JNK, reduced levels of IL-10 may have significant implications on the inflammatory processes in the CNS.
IL-10 therefore has a major anti-inflammatory role in the CNS which is required for CNS homeostasis and normal functioning. Survival of glial and neuronal cells is to some extent dependent on IL-10 as it augments neurotrophic factors. Reduced levels of IL-10 may imply an increase in the synthesis of certain cytokines such as IL-1β, IL-8, IL-6, IL-12, and TNF-α.
Interestingly, another study has reported changes in IL-10 in the CSF of Chronic Fatigue Syndrome patients, and these were increased. This finding is in contrast to our present findings and this may be due to the heterogeneity of the disease, different analytical methods, and the presence of divergent patient subgroups.
Further studies may be required to identify and/or confirm whether the putative IL-10 deficiency may contribute to increased pro-inflammatory activities in CFS.
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