Increasing frailty in RRMS patients linked to higher IL-6 levels: Study
Potential impact found with signaling molecule tied to inflammation
The signaling molecule interleukin-6 (IL-6), which is involved in inflammation, is associated with increasing frailty in people with multiple sclerosis (MS), a new study from researchers in China reported.
Elevated levels of IL-6 significantly correlated with higher scores on a frailty index that measures health deficits across multiple domains, according to the scientists, who noted that their findings “highlight the crucial involvement of inflammatory responses in the pathogenesis [disease development] of MS.”
Additionally, other molecules from the same category of inflammatory signaling proteins, called cytokines, were found to be present at higher levels in individuals with relapsing-remitting MS (RRMS) who were frail than in those who weren’t.
“These results underscore the potential impact of inflammatory responses on frailty development in MS,” the researchers wrote.
More work in this area is needed to allow the development of better tools to assess frailty among people with MS, especially for those in whom the condition may be worsening, according to the team.
“Chronic inflammation is considered a pivotal mechanism underlying the onset of frailty,” the researchers wrote.
The study, “Association between frailty and inflammatory cytokines in patients with multiple sclerosis: a case-control study,” was published in the journal Cytokine.
Investigating how inflammation ties to increasing frailty in MS
Frailty is the condition of bodily and cognitive decline that typically occurs during aging, though other health-related factors may influence the process. It involves multiple biological systems becoming dysregulated and reflects a general increase in the body’s vulnerability to stressors.
People with MS, a progressive neurodegenerative disease, tend to experience frailty at earlier ages than the non-MS population, studies have shown. In patients, frailty is associated with lower quality of life, increasing falls, and more severe MS symptoms.
As MS progresses, the immune system attacks myelin, the protective fatty sheath surrounding nerve cells, disrupting the transmission of signals between the brain and the rest of the body. This immune response causes inflammation in the central nervous system.
Inflammation and oxidative stress — cellular damage caused by harmful molecules in the body — can contribute to frailty, with generalized inflammation “potentially influencing its development,” according to the researchers.
The team suggested that understanding how inflammation is linked to frailty could help in finding new ways to improve health and quality of life for people with MS.
In this study, the scientists examined the relationship between frailty and the levels of various cytokines in the blood.
“We hypothesize higher inflammation levels in weak MS patients, warranting investigation into the association between frailty and peripheral serum [circulating serum] cytokines in MS,” the team wrote.
New tools needed for evaluating symptom severity: Researchers
A total of 83 people with RRMS — a form of the disease characterized by episodes of symptom flare-ups followed by periods of partial or complete recovery — were recruited for the study. The participants were mainly female (79.6%) and had an average age of 48.6.
Compared with 100 controls — participants without MS but with similar age and sex characteristics — the RRMS patients had significantly higher levels of several cytokines, including IL-6, in their blood, the scientists found.
The team then further split the RRMS group into frail and non-frail participants based on frailty index scores, which indicated the degree of dysfunction across 36 survey items. Frail participants were those who had deficits in at least 20% of the items of interest. These individuals had significantly worse MS-related disability, as measured using the Expanded Disability Status Scale (EDSS).
Levels of IL-6 and certain other cytokines were higher in RRMS patients with frailty than in those without, “suggesting a potential role of inflammatory response in frailty pathogenesis,” the researchers wrote. Moreover, the team noted a significant correlation between the level of IL-6 and the frailty index score. Specifically, greater frailty was associated with higher IL-6 levels.
Future efforts should prioritize the development of advanced tools to assess frailty in MS patients, with a specific emphasis on inflammation.
While none of the other cytokines correlated significantly with frailty, higher levels of a cytokine called tumor necrosis factor-alpha (TNF-alpha) correlated with greater EDSS disability. According to the researchers, this further supports the role of inflammation in MS-related disease processes.
“These results suggest that serum cytokine levels may indicate the severity of MS,” the researchers wrote.
Given the methodology of the study, the scientists could not conclude whether IL-6 and other cytokines caused disease progression and frailty or if high levels resulted from these processes.
“Future efforts should prioritize the development of advanced tools to assess frailty in MS patients, with a specific emphasis on inflammation,” the researchers wrote.
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