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

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; ε² = 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).