Research abstract:
Background: Chronic Fatigue Syndrome, also known as Myalgic Encephalomyelitis (CFS/ME), is a debilitating condition that presents with a range of symptoms, including fatigue, cognitive dysfunction, muscular and joint pain, and may be immune-mediated. In particular, patients exhibit abnormal cytokine expression.
Similarly, in Multiple Sclerosis (MS), patients display neuroimmunological symptoms, and abnormal cytokine expression, with some overlap in symptomology with CFS/ME. The purpose of this study was to compare Th1, Th2, Th17 cytokines, inflammatory cytokines and chemokines, in healthy controls, CFS/ME and MS patients.
Methods: Serum samples were collected from healthy controls (n = 16, mean age = 50 ± 11.85 years), CFS/ME patients (n = 16, mean age = 49.88 ± 9.54 years) and MS patients (n = 11, mean age = 52.75 ± 12.81 years). The concentrations of 27 cytokines (IFN-γ, TNF-α, IL-12, IL-2, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-5, IL-17, IL-1ra, IL-7, IL-8, IL-9, eotaxin, IP-10, MCP-1, MIP1α, MIP1β, PDGF-bb, RANTES, basic FGF, GCSF, GMCSF, VEGF and IL-15) were measured using a Bio-Plex Pro™ kit.
Results: IFN-γ, IL-10 and IL-5 were significantly higher in the serum of both CFS/ME and MS patients compared to the healthy controls (p ≤ 0.041). However, only the MS patients had significantly elevated levels of IL-12, IL-1β, IL-4, IL-13, IL-6, IL-17, IL-1ra, IL-7, IL-9, eotaxin, IL-10, MIP1α, basic FGF, GCSF and VEGF compared to the CFS/ME patients and controls (p ≤ 0.04). There were no significant differences between groups for IL-8, MCP-1, MIP1β, RANTES, GMCSF, TNF-α, and IL-2.
Conclusion: CFS/ME and MS patients both displayed abnormal cytokine levels, with dual expression of Th1 and Th2 cytokines. Further research into cytokines such as IFN-γ, IL-10 and IL-5, with the use of a specific CFS/ME case definition and sensitive cytokine assays, is required to improve the understanding of the pathophysiology of CFS/ME.
Conclusion to paper:
In conclusion, this study has reported expression of Th1 and Th2 cytokines in CFS/ME and MS patients. Elevated levels of IFN-γ, IL-10 and IL-5 were found in both CFS/ME and MS. In the MS cohort, the results were consistent with the majority of findings from previous studies, where general elevation of pro-inflammatory, some anti-inflammatory, Th1 and Th2 cytokines has been observed [102].
However, results for CFS/ME cytokine levels, including IFN-γ [37] [103], IL-10 [6] [10], IL-17 [8], and IL-12 [6] [8], conflicted with previous findings. This is likely due to the heterogeneity of CFS/ME [102]. Additionally the use of the ICC [1] as opposed to the more commonly used 1994 CDC definition [104], may have played a role in differential results.
A study comparing the results of cytokines across differing definitions could help resolve conflicting findings of previous studies. Additionally different subgroups of CFS/ME, based on symptomology and severity, may present with differing cytokine profiles, and this may be an area for future research.
A longitudinal study with multiple time points would be more suitable to assess cytokine profiles. Furthermore isolation of immune cells to determine specific cytokine secretion from different cell types may provide more detailed insight into CFS/ME pathophysiology.
Lastly CFS/ME patients are known to administer multiple medications, which may affect cytokine secretion. Analysis of these interactions and effects could be an important area for further research.
A comparison of Cytokine profiles of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis patients, by N Wong, T Nguyen, E Brenu, S Broadley, D Staines and S Marshall-Gradisnik in International Journal of Clinical Medicine vol 6, pp 769-783.
