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New paper: Cytokines in Cerebrospinal Fluids of Patients with ME/CFS

Countrygirl

Senior Member
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5,431
Location
UK
http://www.hindawi.com/journals/mi/2015/929720/

I am late on PR tonight and this must be posted somewhere, so I apologise if I am double-posting.

Cytokines in the Cerebrospinal Fluids of Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
D. Peterson,1 E. W. Brenu,2 G. Gottschalk,1 S. Ramos,2 T. Nguyen,2 D. Staines,2 and S. Marshall-Gradisnik2

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Discussion
In the CNS, microglial cells have the capacity to secrete cytokines, act as antigen presenting cells, and induce phagocytosis [20, 2325]. These cells may have either protective or pathological effects on the CNS function. The cytokines produced by the microglial cells include IL-4, IL-10, IL-6, IL-13, and IFN-γ [21].

The present pilot study has shown that cytokine IL-10 was significantly decreased in the CFS/ME patients. IL-10 is secreted by almost all cells of innate and adaptive immune system and it protects autoreactive and inflammatory reactions by dampening Th1 immune related responses. IL-10, previously described as a cytokine synthesis inhibitory factor, displays immunoregulatory as well as immunostimulatory activities, prevents autoreactivity [26] and T cell proliferation, and protects against autoimmunity [27]. Additionally IL-10 reduces B7-2 and CD28 signalling, inhibits nitric oxide secretion, degrades cytokine related mRNAs, and decreases the expression of MHC II molecules [2830]. Importantly, IL-10 has positive and negative effects on several signalling pathways that are related to the Janus kinase/signal transducer and activator of transcription; hence, modulations in IL-10 may affect inflammatory signals and cellular process in the CNS [31]. Antigen presenting cells particularly macrophages and dendritic cells produce IL-10; this is important during inflammatory response to sepsis and infection [32]. Myeloid derived IL-10 regulates the function of T cells and the production of IL-10 by antigen presenting cells [32]. Hence, reduced levels of IL-10 may suggest compromises to the function and regulation of these cells. Microglia are the predominant myeloid cells in the brain and are known to produce IL-10 [33]. Compromises to these cells may contribute to the low levels of IL-10 observed in this pilot study.

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 [34]. 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 [35]. 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 [36]. However, we did not observe a substantial increase in the levels of these cytokines in the CNS; hence, other mechanisms may be acting to compensate for the reduced levels of IL-10. Only one study has reported changes in IL-10 in the CSF of CFS/ME patients, and these were increased [37]. 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. Nonetheless, a decrease in CNS IL-10 may be related to symptoms of fever reported in the CFS/ME cases [38] and this may be important for future investigations.

Whether or not the profile of cytokines in the CNS is similar to that in the periphery remains to be determined. Further studies are therefore required with larger samples to determine the role of CNS cytokines in CFS/ME.