Premium
IL‐1R Activation Undermines Respiratory Plasticity
Author(s) -
Hocker Austin Dean,
Huxtable Adrianne G
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1055.14
Subject(s) - inflammation , respiratory system , medicine , lipopolysaccharide , respiratory center , hypoxia (environmental) , muscles of respiration , receptor , immunology , anesthesia , pharmacology , chemistry , organic chemistry , oxygen
Despite a pervasive role for inflammation in ventilatory control disorders, we are only just beginning to understand the mechanisms by which inflammation undermines respiratory plasticity. Interleukin‐1 (IL‐1) signaling regulates plasticity in other central nervous system regions; promoting central pain in the spinal dorsal horn and inhibiting plasticity in the hippocampus. Thus, we tested the hypothesis that IL‐1 receptor (IL‐1R) activation during systemic inflammation undermines phrenic long‐term facilitation (pLTF), a model of respiratory plasticity induced by acute intermittent hypoxia. pLTF is reduced 24 hours after lipopolysaccharide (LPS; 100 mg/kg; i.p.) compared to control (12 ±8%, n=5; 57 ± 10%, n=6; respectively), similar to previously published studies. Importantly, pLTF is restored by peripheral IL‐1R antagonism (64 ± 6%; n=6; AF‐12198, i.p. 0.5 mg/kg, 24 hours) after LPS. Acute, spinal IL‐1R antagonism (1 mM AF‐12198 in aCSF; 15 mL; intrathecal) also restored pLTF (52 ± 16%; n=2) compared to LPS treated rats (9 ± 8%; n=3). These data suggest both peripheral and spinal IL‐1Rs play important roles in undermining pLTF after systemic inflammation. Understanding the inflammatory mechanisms inhibiting respiratory plasticity is crucial to developing treatment strategies to promote breathing during ventilatory control disorders. Support or Funding Information Supported by Francis Families Foundation (AGH) and University of Oregon.