Treadmill Exercise Modulates TNF‐α and IL‐1β Expression in Rodent Models of CNS Inflammation: A Systematic Review

ABSTRACT Neuroinflammation contributes to the progression of central nervous system (CNS) disorders, with tumour necrosis factor‐alpha (TNF‐α) and interleukin‐1 beta (IL‐1β) recognized as key pro‐inflammatory mediators. This systematic review synthesized findings from 17 preclinical studies (26 observations) examining the effects of treadmill exercise on TNF‐α and IL‐1β expression in the brain tissue of male rodents (rats and mice). Cytokine responses were standardized as log₂ fold change to enable cross‐study comparison. Exercise intensity showed a significant association with cytokine reduction (Kruskal–Wallis p = 0.0165; ε 2 = 0.270), with greater reductions under vigorous versus light protocols (Dunn's p _adj = 0.0137). There were no significant differences by duration ( p = 0.847), marker (TNF‐α vs. IL‐1β; p = 0.227) or species (rats vs. mice; p = 0.501). In neurodegenerative models, a significant marker‐by‐intensity interaction emerged (two‐way ANOVA, p = 0.0039); moderate showed the largest overall reduction (Kruskal–Wallis p = 0.016; Dunn's p _adj = 0.0158 vs. light), whereas vigorous showed no additional benefit ( p _adj ≥ 0.1056). These findings suggest that treadmill exercise may modulate neuroinflammatory signalling in the rodent brain, with exercise intensity emerging as a key moderator candidate supported by consistent evidence; however, the optimal dose appears context‐dependent (pooled: vigorous > light; neurodegenerative models: moderate maximal). Interpretation should be cautious because the body of evidence derives from male‐only samples, heterogeneous methods and several SYRCLE domains with frequently unclear ratings (randomization, allocation concealment, blinding, housing).