Fig. 1

Signaling involving TLR2 and TLR4 in strenuous and moderate aerobic exercise. Excess physical exercise increases LPS levels and contributes to TLR2, TLR4, and NF-kB upregulation. As a consequence, there is an increase in circulating pro-inflammatory cytokines. Stimuli of exercise stress transmit nerve impulses to the brain, raising the levels of counter-regulatory hormones such as cortisol. Accordingly, high mitochondrial oxidative stress induced by strenuous aerobic exercise causes excessive intracellular ROS formation that also upregulates NF-kB expression, intensifying the acute inflammation state. Under these excessive stress conditions, adaptive immunity can be triggered by the increase in costimulatory molecules in antigen-presenting cells, thus activating T cells. In contrast, the regular physical exercise of moderate intensity reduces LPS, TLR2, TLR4, and NF-kB expression. Under these conditions, NF-kB does not translocate to the cell nucleus. Instead, the anti-inflammatory pathway PI3K/AKT/mTOR is activated, promoting the production of anti-inflammatory cytokines such as IL-10 that inactivate TNF-α. Physical exercise at a moderate intensity also has a compensatory effect against the exacerbated production of reactive oxygen and nitrogen species responsible for the oxidative damage. Elevated production of IGF-1 is observed after exercise. IGF-1 provides an anti-inflammatory effect on the skeletal muscle cells, reducing the expression of the pro-inflammatory cytokines through a decrease of TLR4 expression