The autonomic nervous system and innate immune system are regarded as systems that can not be voluntarily influenced. We evaluated the effects of a training program on the autonomic nervous system and innate immune response.

Volunteers were randomized to either the intervention (n=12) or control group (n=12). Subjects in the intervention group were trained for 10 days (including breathing techniques [cyclic hyperventilation followed by breath retention] and exposure to cold [i.a. immersions in ice cold water]). The control group did not receive training. Subsequently, all subjects underwent experimental human endotoxemia (i.v. administration of 2 ng/kg E. Coli endotoxin).

In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in significantly increased plasma epinephrine levels (2.08±0.37 vs. 0.35±0.06 nmol/L, p<0.0001). In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels (r=0.82, p=0.001), and were higher (peak levels of 791 [498-1203] vs. 261 [187-684] pg/mL, p=0.01). Levels of pro-inflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels (peak levels of 213 [169-553] vs. 456 [281-746] pg/mL, p=0.02; 284 [157-344] vs. 471 [316-703] pg/mL, p=0.01; 368 [266-540] vs. 562 [422-647] pg/mL, p=0.004, respectively; r=-0.71, p=0.01; r=-0.59, p=0.045; r=-0.71, p=0.01). Finally, endotoxin-induced flu-like symptoms were lower in the intervention group (peak symptom score of 3.8±0.5 vs. 8.6±0.6, p<0.0001).

In conclusion, we demonstrate for the first time that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo.