EFFECTS OF AEROBIC AND RESISTANCE TRAINING ON IMMUNE FUNCTION IN MULTIPLE SCLEROSIS

Multiple Sclerosis (MS) is recognized as a chronic immune-mediated, inflammatory, and neurodegenerative disorder of the central nervous system (CNS) characterized by axonal damage that disrupts neural conduction. The neurodegenerative nature of this neurological disease manifests through a wide spectrum of debilitating symptoms, including muscle weakness, fatigue, loss of balance, speech impairment, diplopia, and cognitive decline. These neurological signs and symptoms vary depending on the anatomical location of the lesions.

As an effective rehabilitation strategy for individuals with MS, exercise manages symptoms, restores function, optimizes quality of life, promotes wellness, and encourages participation in activities of daily living. Previous studies have demonstrated that aerobic activity is inversely associated with MS symptoms, exerting protective and potentially restorative effects. Furthermore, growing evidence suggests that exercise can be considered a disease-modifying therapy in MS. Although reductions in aerobic capacity and endurance are not primary clinical features of MS, they frequently develop as secondary manifestations. Therefore, strategies designed to enhance aerobic endurance and capacity, such as aerobic exercise, are highly valuable in MS management. Consequently, aerobic-based exercise interventions are frequently utilized in the therapeutic management of MS to improve aerobic endurance and capacity. Aerobik exercise is a modality designed to stress the cardiovascular system through continuous, rhythmic engagement of large muscle groups (e.g., jogging, walking, swimming, rowing, and cycle ergometry).

The anti-inflammatory effect of aerobic exercise may prevent systemic inflammatory progression. Exercise counteracts inflammation by reducing adipose tissue mass, which promotes the polarization of macrophages toward an anti-inflammatory state, thereby limiting cytokine production. Additionally, the downregulation of toll-like receptors associated with decreased inflammatory monocytes occurs. The inflammatory state is also modulated in response to exercise stimulation by increased levels of skeletal muscle-derived interleukin-6 (IL-6) and the prevention of sustained cytokine release associated with obesity. Cytokines, critical components of MS pathophysiology, are protein hormones that regulate communication between the innate and adaptive branches of the immune system. In healthy populations, a homeostatic balance exists among T-helper cytokines; however, this balance is altered in MS, reflecting increased proinflammatory cytokines (IL-1, IL-6) and decreased anti-inflammatory cytokines (IL-10). These aberrations can accelerate myelin destruction in the brain and spinal cord. Data regarding the effects of physical activity on the immune system in MS remain limited. Cytokines, the primary focus of exercise-based MS studies, encompass a spectrum of proinflammatory cytokines, including IL-1, IL-2, IL-6, IL-17, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). Most of these cytokines are well-documented contributors to MS pathogenesis.

Recently, there has been a growing interest in resistance exercise training. Resistance training studies in individuals with MS have reported improvements in leg strength, reductions in perceived fatigue, and increases in muscle power. Resistance training protocols in this population have generally been of low-to-moderate intensity, typically utilizing progressive resistance exercise ranging from 60% to 80% of the maximum voluntary contraction.

The aim of this study is to conduct a randomized controlled trial to investigate the EFFECTS OF AEROBIC AND STRENGTHENING EXERCISES ON THE IMMUNE SYSTEM AND FUNCTIONALITY IN INDIVIDUALS DIAGNOSED WITH MULTIPLE SCLEROSIS.

Inclusion criteria

• Diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS). Aged between 19 and 45 years. Expanded Disability Status Scale (EDSS) score between 0.5 and 3.5. Not currently receiving steroid therapy (or having no recent corticosteroid treatment within the specified washout period).

Exclusion criteria

• Having a high baseline level of physical activity.

Experiencing an acute MS relapse or having a history of a relapse within the past 3 months.

Presence of any orthopedic or bone pathology that would prevent participation in the exercise program.

Concomitant diagnosis of any known neuromuscular or immunological disease other than MS.

Initiating immunomodulatory therapy within the last 6 months.

Presence of visual involvement or symptomatic diplopia.

High-grade lower extremity spasticity, defined as a Modified Ashworth Scale (MAS) score of 3 or 4.

Abnormal white blood cell (WBC) count outside the normal reference range of 4,000-10,000 cells/µL.

Presence of any severe cardiopulmonary condition that would contraindicate or prevent participation in physical exercise.