Vagal nerve stimulation attenuates IL-6 and TNFα expression in respiratory regions of the developing rat brainstem

• Interleukin-6 (IL-6) is up-regulated in the brainstem via intratracheal injection of Lipopolysaccharide (LPS).
• Tumor necrosis factor alpha (TNFα) is also up-regulated in the brainstem via intratracheal injection of LPS.
• Vagal nerve stimulation (VNS) attenuates the up-regulation of these cytokines after LPS.

Pre-term infants are at greater risk for systemic infection due to an underdeveloped immune system. Airway infection results in immune up-regulation of early pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) in the brainstem. Current treatment for neonatal infection involves antibiotic administration. We previously showed that LPS injected into the trachea of neonatal rats causes changes in breathing and in IL-1β expression in the nucleus tractus solitarii (NTS) and hypoglossal motor nucleus (XII). We hypothesize that lipopolysaccharide (LPS) instilled in the trachea also causes the up-regulation of IL-6 and TNFα in the brainstem autonomic control regions. To test this hypothesis we injected LPS into the trachea of rat pups (postnatal ages 10–12 days) and then assessed changes in IL-6 and TNFα. Vagal nerve stimulation has been used in the treatment of many inflammatory disorders, including sepsis. Our experiments show that VNS attenuates the upregulation of IL-6 and TNFα caused by LPS and may be a viable alternative to antibiotics.