Document Type : Original Article
Authors
1 MS.c Student in Exercise Physiology, Faculty of Education and Psychology, Azarbaijan Shahid Madani University, Tabriz, Iran.
2 Associated Professor at Department of Sport Sciences, Faculty of Education and Psychology, Azarbaijan Shahid Madani University, Tabriz, Iran.
Abstract
Extended Abstract
Background and Aim: There is evidence that components of the innate immune system, particularly the complement system, play a role in multiple sclerosis (MS) (1, 2). The complement system, a key element of innate immunity (1), consists of blood proteins involved in inflammation and host defense. C3 and C4 are potential diagnostic markers for autoimmune inflammatory demyelinating diseases of the central nervous system (CNS). Their activation is central to the complement system and contributes to neurodegeneration in MS (4, 7). Studies have shown that plasma levels of C3 and C4 are elevated in MS patients compared to healthy controls (2). In addition to pharmacological treatments, lifestyle modifications, such as physical activity, can effectively modulate the complement system without adverse effects. Therefore, the aim of this study was to investigate the effects of combined physical C3 and C4, the C3/C4 ratio and motor function in women with multiple sclerosis.
Materials and Methods: The present study employed a pretest-posttest design involving 30 patients aged 30 to 40 years who were diagnosed with multiple sclerosis (MS) according to the McDonald 2010 criteria. Participants were randomly assigned to two groups: an experimental group (n=15) that participated in an exercise program and a control group (n=15) that went about their normal daily activities. The inclusion criteria required an Expanded Disability Status Scale (EDSS) score of less than five, as determined by a neurological examination by a physician (20). Participants had to be able to move independently and voluntarily consent to participate in the study. Exclusion criteria included inflammatory conditions such as metabolic syndrome, cardiovascular problems (including hypertension), kidney problems, asthma, potential neuropathic pain in the lower extremities, severe cognitive impairment, visual impairment, drug dependence (alcohol or smoking), comorbidities that could interfere with participation, recent MS relapses within the last eight weeks, pregnancy or regular exercise in the last six months (21). Blood samples and motor function assessments were taken 72 hours before and after the training protocol in a fasting state. C3 and C4 levels were measured using the turbidometry method. Motor function was assessed with the timed up and test (TUG) and the balance test (FTSST). The exercises protocol followed the American College of Sports Medicine (ACSM) guidelines for patients with MS (26). The program lasted 12 weeks, with sessions taking place three days a week and lasting approximately one hour each. It included: a) aerobic exercise at 40-60% of maximum heart rate (MHR), b) resistance exercises with a yellow band consisting of three sets of eight to fifteen repetitions, c) balance exercises in standing and dynamic positions, and d) seated stretching exercises with controlled breathing, based on methods from previous studies. The data were analyzed using analysis of covariance with the significance level of p<0.05.
Findings: At baseline, an independent t-test showed that the initial characteristics of weight (experimental group: 65.41±11.70 kg; control group: 58.58±12.68 kg; p=0.72) and MS history (experimental group: 51.75±3.30 years; control group: 21.83±6.30 years; p=0.66) were similar in both groups. After 12 weeks of combined training, the experimental group showed a significant reduction in serum levels of complement C3 compared to the control group (p=0.01). However, there were no significant differences between the groups in complement C4 levels or the C3/C4 ratio (p>0.05). In addition, the experimental group showed significant improvements in motor performance, (fall risk and balance), as well as a significant reduction in walking times compared to the control group (p<0.05) (Table 1).
Conclusion: The current evidence on the effects of exercise on complement components C3 and C4 in individuals with MS remains limited and somewhat conflicting. One review found that the C3 and C4 family proteins are the best studied. Complement proteins were found to be transiently activated immediately after acute exercise and remain elevated for up to 72 hours after strength training and ultra-endurance running. Conversely, prolonged exercise and higher cardiorespiratory fitness levels are associated with a decrease in C3 family proteins (32). The response of complement proteins depends on the type of exercise. Endurance exercise tends to decrease C3 and increase C4, while anaerobic (fast) exercise reduces C4(12). The observed decrease in C3 following combined training may be due to a reduction in inflammatory mediators that activate the complement cascade. Combined training (strength and endurance training) has been shown to improve motor function and reduce inflammation in women with MS (36). In contrast to acute exercise, exercise reduces inflammatory proteins that activate the complement system, such as C-reactive protein (CRP), as well as cells such as monocytes that secrete these proteins (32). In this study, combined exercises were more effective in improving balance. Conversely, in studies that did not show significant improvements in balance, balance exercises alone were found to be insufficient (30). As for the effects of breathing exercises on the immune system, research in psychoneuroimmunology suggests that these exercises may alter immune markers and promote health by modulating the adrenocorticotropin-cortisol immune pathway (40). Overall, the combination of resistance, aerobic, balance, and breathing exercises appears to enhance both immunological and functional outcomes in individuals with MS. These findings support the recommendation of such multifaceted exercise programs as a beneficial non-pharmacological intervention for this population.
Ethical considerations: Before starting the protocol, a consent form was signed by the subjects and an ethics ID number IR.AZARUNIV.REC.1402.014 was obtained.
Conflict of interest: There are no conflicts of interest.
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