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

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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.

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