Patients with multiple sclerosis who were obese had higher EDSS scores and higher levels of inflammatory IL-6 and leptin in the CSF prior to treatment, as well as lower levels of anti-inflammatory IL-13.
Mario Stampanoni Bassi, MD
There has been a growing body of literature showcasing the association between metabolic pressure, autoimmunity, and neurodegeneration in chronic inflammatory conditions and new findings suggest that obesity and an altered lipid profile may be related to both aggravated central inflammation and higher clinical disability in patients with relapsing multiple sclerosis (MS).
The single-site, cross-sectional study needs to be confirmed, the investigators noted, but the analysis showed a positive correlation between body mass index (BMI) and Expanded Disability Status Scale (EDSS) score in 140 patients with MS. The patients who were obese (BMI >30; n = 24) prior to therapeutic intervention had higher EDSS scores (median, 3; IQR, 2 to 3.4) than those with a normal BMI (18.5 to 24.9; n = 83; median, 1.5; IQR, 1 to 2.75; B-H adjusted P = .015).
“Overall, these findings could provide new therapeutic opportunities aimed at limiting the negative impact of altered lipid metabolism on inflammatory response in MS, representing useful adjunctive strategies to modify the course of this potentially devastating disease,” the authors, led by Mario Stampanoni Bassi, MD, of the Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, wrote.
Bassi and colleagues noted that the elevated EDSS in obese patients with MS was driven by an increased likelihood of pyramidal system involvement, which was 29% for normal weight patients compared to 42% and 54% for those who were overweight and obese, respectively (P = .02). No other functional systems and BMI were significantly associated, nor were any of the few correlations BMI showed with serum lipids after adjusting for clinical variables.
When exploring the association between BMI and interleukin-6 (IL-6) and leptin, 2 proinflammatories, as well as IL-13, an anti-inflammatory, the investigators observed significantly different levels of cerebrospinal fluid (CSF) IL-6 between the 3 BMI groups when adjusting for sex, age, disease duration, smoking, and the presence of radiological activity (ANCOVA main effect: F(2, 132), 3.84; P = .024). Additionally, post hoc analysis showed that obese patients had higher CSF levels of IL-6 than normal-weight patients (B-H adjusted P = .029). IL-13 was shown to be lower in patients with MS who were obese compared with normal-weight patients (B-H adjusted P = .021).
“The relationship between altered lipid metabolism and inflammation highlights the key role of adipocytokines in the cross talk between metabolism, immunity, and neurodegeneration,” Bassi and colleagues wrote. Similar to what was seen with IL-6, post hoc comparisons showed that the obese MS group reported higher leptin CSF concentrations than those of normal-weight patients with MS (B-H adjusted P <0.001).
“Enhanced CSF levels of proinflammatory molecules could promote disease reactivations and neurodegeneration in MS and may represent the pathophysiological mechanism underlying the worse disease course observed in obese MS patients,” the investigators wrote. They added that the lower expression of the anti-inflammatory IL-13 is suggestive of its role in exacerbating MS disease severity in obese patients. “It has been previously shown that IL-13 may exert neuroprotective effects in MS, reducing glutamate-mediated excitotoxicity.”
The group did acknowledge some limitations of the study, most notably a lack of prospective measures of clinical disability and neuronal damage. They added that its single-center and cross-sectional nature requires further confirmation of the data.
Bassi MS, Iezzi E, Buttari F, et al. Obesity worsens central inflammation and disability in multiple sclerosis. Mult Scler J. Published online June 4, 2019. doi: 10.1177/1352458519853473.