Paraganglia of the vagus (Xth cranial) nerve are minute clusters of glomus cells resembling the carotid body – an organ that senses changes in blood chemistry. They are chemosensitive to cyanide and reductions in the partial pressure of oxygen (PO₂) (O’Leary et al., 2004). We proposed that they may also be sensitive to circulating cytokines released from exercising muscles. Specifically, we wished to test our hypothesis that the myokine- interleukin-6 (IL-6) can cause an acute change in superior laryngeal nerve (SLN) activity. We exposed isolated superfused rat glomus cells – located at the bifurcation of the SLN – to hypoxia (~20mmHg) to measure chemosensitivity to changes in PO2. Next, we exposed the cells to IL-6 at concentrations of 0.1ng/ml, 0.3ng/ml and 1ng/ml during both normoxia (~100mmHg) and hypoxia while monitoring single axonal action potential frequency. This was followed by hypoxia in the absence of IL-6 to check that the preparation was still responsive. One single fibre per animal was tested and values are expressed as mean ± S.E.M. The results confirm previous findings that these cells respond strongly to changes in PO₂, significantly increasing their discharge rate in response to hypoxia (from 0.71 ± 0.36 to 6.0 ± 2.4Hz). IL-6 did not affect the baseline discharge rate of the SLN units at any concentration; however, it did modulate the response to hypoxia. In 5/6 animals the smallest IL-6 concentration (0.1ng/ml) caused a small increase in peak frequency of the SLN (mean peak frequency 6.6 ± 2.6 Hz). Also, in 5/6 animals the largest IL-6 concentration (1ng/ml) caused a decrease in peak frequency of the SLN (4.7 ± 2.1 Hz). There was a statistically significant difference in peak discharge from the lowest to the highest concentration of IL-6 (Wilcoxon signed-rank test, p=0.03). This data shows that although the myokine IL-6 has no effect on basal discharge of rat vagal paraganglia during normoxia, it can modulate hypoxic responses. Therefore IL-6 may not play a role in modulating discharge during exercise when active muscles release it, but rather modulate discharge when paraganglia become inflamed, e.g. during chronic hypoxia (Liu et al., 2009).