IL-6 and TNF-α responses to acute and regular exercise in adult individuals with multiple sclerosis (MS): a systematic review and meta-analysis

Abstract

Background In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls. Method We performed an online search via PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library till September 2021 to identify original studies on IL-6 and TNF-α changes after acute and regular exercise in PwMS and controls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 original studies were included in the meta-analysis. Sensitivity analyses were used to identify the origins of heterogeneity. R 4.0.4 was used to perform the meta-analysis of IL-6 and TNF-α levels before and after acute and regular exercise in PwMS, compared to controls. This study does not qualify for a clinical trial number. Results IL-6 levels did neither increase nor decrease after acute and regular exercise in PwMS, and compared to controls (pre- vs. post-intervention: Standardized Mean Difference (SMD) -0.09, 95% CI [−0.29; 0.11], p-value = 0.37, PwMS vs. Control: SMD −0.08, 95% CI [−0.33; 0.16], p-value = 0.47). In PwMS, TNF-α levels decreased after regular exercise and when TNF-α levels of both acute and regular exercise were pooled (pre- vs. post-intervention: SMD −0.51, 95% CI [-0.91; 0.11], p-value = 0.01, PwMS vs. Control: SMD −0.23, 95% CI [−0.66; 0.18], p-value = 0.26). TNF-α levels did neither increase nor decrease after acute and regular exercise in PwMS, when compared to controls. Conclusion This systematic review and meta-analysis show that exercise does not lead to significant changes in peripheral levels of IL-6 in PwMS in contrast to the observed response in healthy subjects and other medical contexts. However, regular exercise had a specific anti-inflammatory effect on blood TNF-α levels in PwMS. It remains to be investigated why PwMS display this different exercise-induced pattern of cytokines.

Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model

“…Moreover, TNF-α disrupted neuronal mitophagy, increased oxidative stress, triggered inflammation, dysregulated GSK-3 β activity, and promoted p-Tau accumulation [ 63 ]. Further, other studies stated that neurodegeneration in patients with T2DM could be considerably lowered by targeting cytokines, cytokine receptors, and nuclear transcription factors linked to inflammation, like IL-6 and TNF- α, alone or in combination [ 48 ]. In this work, pramlintide and liraglutide exhibited anti-inflammatory effects through significantly decreasing the inflammation markers: serum IL-6 and hippocampal TNFα expression when compared to the diabetic group.…”

Preventive exercise and physical rehabilitation promote long‐term potentiation‐like plasticity expression in patients with multiple sclerosis

“…Exercise may exert immunomodulatory effects in MS [37, 38]. Preventive exercise in experimental autoimmune encephalomyelitis (EAE) has been associated with increased expression of regulatory T cells, reduced activation of peripheral and brain resident immune cells, and decreased production of proinflammatory cytokines [39].…”

Multiple sclerosis and exercise—A disease-modifying intervention of mice or men?

“…However, whether biological and physiological responses to exercise differ in the context of immune dysregulation is not clear. For example, one meta-analysis found that, in contrast with controls, neither acute nor regular exercise led to a significant change in peripherally circulating IL-6 in pwMS ( 29 ). Moreover, whether the immunomodulatory changes that occur in the context of exercise might have a clinically meaningful impact on the disease course in MS requires specific studies.…”