Synergistic effects of intradialytic concurrent training and melatonin supplementation on immune cell adaptations in hemodialysis patients

BACKGROUND: Immune dysfunction and chronic low-grade inflammation contribute substantially to morbidity and cardiovascular risk in patients undergoing hemodialysis (HD). Both exercise-based interventions and melatonin supplementation have demonstrated immunomodulatory and anti-inflammatory potential; however, their combined long-term effects remain unclear. This study investigated whether a 12-week intradialytic concurrent training (ICT) program with melatonin supplementation could improve hematological and immune cell profiles in HD patients. METHODS: Thirty HD patients were randomly allocated to ICT with melatonin (ICT-MEL), ICT with placebo (ICT-PLA), or control with placebo (C-PLA). ICT groups trained three times per week. During the intervention, participants received either 3 mg of melatonin (ICT-MEL) or placebo (ICT-PLA and C-PLA) nightly before nocturnal sleep. Pre- and post-intervention blood samples were analyzed for hematological parameters, adaptive lymphocyte subsets (CD4⁺ T cells, CD8⁺ T cells, and B cells), innate lymphocytes (natural killer [NK] cells), and monocyte subsets. RESULTS: Hematological measures remained stable from pre-to post-intervention across all groups. In contrast, the ICT-MEL intervention induced significant within-group improvements in T-cell immunity, including increases in CD4⁺ percentage (p = 0.007), CD8⁺ T-cell count (p < 0.05), and CD8⁺ percentage (p < 0.001), accompanied by a decrease in the CD4⁺/CD8⁺ ratio (p < 0.05). One-way ANOVA of Δ changes confirmed a significantly greater reduction in the CD4⁺/CD8⁺ ratio in ICT-MEL compared with both ICT-PLA and C-PLA (p < 0.05), along with greater increases in CD4⁺ percentage, CD8⁺ count, and CD8⁺ percentage. Following the intervention, CD4⁺ T-cell count was significantly higher in the ICT-PLA group compared with the C-PLA group (p < 0.05). B-cell percentage increased significantly from pre-to post-intervention only in the ICT-PLA group (p = 0.017), with post hoc analyses indicating a greater increase compared with C-PLA (p < 0.05). NK-cell counts and percentages remained unchanged across all groups. Notably, intermediate monocytes (CD14⁺⁺CD16⁺) decreased significantly from pre-to post-intervention in the ICT-MEL group in both absolute count (p = 0.02) and percentage (p = 0.017), while classical and non-classical monocyte subsets showed no significant changes. CONCLUSION: ICT combined with melatonin supplementation was associated with favorable changes in immune cell populations in patients undergoing HD, including improved T-cell profiles and reduced intermediate monocyte subsets. These findings suggest potentially beneficial immunological adaptations and are consistent with a synergistic effect of exercise and MEL supplementation in this population.