Viral‐Induced Systemic Inflammation Undermines Respiratory Motor Plasticity

Systemic inflammation arises from varied stimuli and elicits distinct inflammatory profiles, yet we know little about the effects of different inflammatory stimuli on respiratory motor plasticity. Bacterial‐induced systemic inflammation undermines respiratory motor plasticity in the form of phrenic long‐term facilitation (pLTF), induced by acute intermittent hypoxia (AIH). pLTF is evoked by distinct cellular mechanisms, such as the Q‐pathway (induced by moderate AIH, PaO 2 35–45 mmHg) and the S‐pathway (induced by severe AIH, PaO 2 25–35 mmHg). The Q‐pathway is undermined by bacterial‐induced inflammation at 3 and 24 hours, while the S‐pathway is resistant. However, the effects of viral‐induced systemic inflammation on pLTF are unknown. Since viral‐induced inflammation is common, we tested the hypothesis that inflammation induced by a viral mimetic polyinosinic:polycitidylic acid (polyIC) would undermine Q‐pathway‐evoked pLTF, but not S‐pathway‐evoked pLTF. PolyIC dose‐response experiments (0.25 – 0.75 mg/kg, i.p.) revealed 0.75 mg/kg polyIC (i.p.) was sufficient to undermine Q‐pathway‐evoked pLTF 24 hours post‐polyIC (17 ± 15% change from baseline, n=5, p > 0.05). However, at 3 hours, polyIC (0.75 mg/kg, i.p.) was not sufficient to undermine Q‐pathway‐evoked pLTF (67 ± 21%, n=5, p < 0.0001), suggesting the temporal actions of viral‐induced systemic inflammation differ from bacterial‐induced systemic inflammation. Confirming the role of inflammatory signaling after polyIC (0.75 mg/kg, 24 hours, i.p.) in impairing pLTF, a non‐steroidal anti‐inflammatory (ketoprofen, 12.5 mg/kg, i.p., 3 hours) restored Q‐pathway‐evoked pLTF (64 ± 24%, n=5, p < 0.0001), and was not different from saline controls (55 ± 13%, n=5, p = 0.4711). Additionally, S‐pathway‐evoked pLTF was insensitive to polyIC‐induced inflammation (0.75 mg/kg, i.p.; 72 ± 25%, n=5, p < 0.0001) and was not different from saline controls (65 ± 32%, n=4, p = 0.6291). Our results suggest the inflammatory‐impairment of Q‐pathway‐evoked pLTF is not stimulus specific and confirm the inflammatory‐resistance of S‐pathway‐evoked pLTF. These data support the hypothesis that S‐pathway‐evoked plasticity could compensate for Q‐pathway impairments during inflammation. Thus, in situations where respiratory motor plasticity may be beneficial, for example, as a therapeutic tool to improve motor function after incomplete spinal cord injury, inflammation likely undermines Q‐pathway‐evoked plasticity and strategies targeting S‐pathway‐evoked plasticity may improve therapeutic outcomes. Support or Funding Information HL141249 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .