title: Systemic LPS induces spinal inflammatory gene expression and impairs phrenic long-term facilitation following acute intermittent hypoxia.
abstract: Although systemic inflammation occurs in most pathological conditions that challenge the neural control of breathing, little is known concerning the impact of inflammation on respiratory motor plasticity. Here, we tested the hypothesis that low-grade systemic inflammation induced by lipopolysaccharide (LPS, 100 μg/kg ip; 3 and 24 h postinjection) elicits spinal inflammatory gene expression and attenuates a form of spinal, respiratory motor plasticity: phrenic long-term facilitation (pLTF) induced by acute intermittent hypoxia (AIH; 3, 5 min hypoxic episodes, 5 min intervals). pLTF was abolished 3 h (vehicle control: 67.1 ± 27.9% baseline; LPS: 3.7 ± 4.2%) and 24 h post-LPS injection (vehicle: 58.3 ± 17.1% baseline; LPS: 3.5 ± 4.3%). Pretreatment with the nonsteroidal anti-inflammatory drug ketoprofen (12.5 mg/kg ip) restored pLTF 24 h post-LPS (55.1 ± 12.3%). LPS increased inflammatory gene expression in the spleen and cervical spinal cord (homogenates and isolated microglia) 3 h postinjection; however, all molecules assessed had returned to baseline by 24 h postinjection. At 3 h post-LPS, cervical spinal iNOS and COX-2 mRNA were differentially increased in microglia and homogenates, suggesting differential contributions from spinal cells. Thus LPS-induced systemic inflammation impairs AIH-induced pLTF, even after measured inflammatory genes returned to normal. Since ketoprofen restores pLTF even without detectable inflammatory gene expression, "downstream" inflammatory molecules most likely impair pLTF. These findings have important implications for many disease states where acute systemic inflammation may undermine the capacity for compensatory respiratory plasticity.
authors: Department of Comparative Biosciences, University of Wisconsin, Madison, WI, USA.
authors: A G
authors: AG
authors: Huxtable
authors: S M C
authors: SM
authors: Smith
authors: S
authors: S
authors: Vinit
authors: J J
authors: JJ
authors: Watters
authors: G S
authors: GS
authors: Mitchell
mesh_terms: D000208:Acute Disease; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D000860:Hypoxia / Q000139:chemically induced / Q000276:immunology*; D008070:Lipopolysaccharides; D017774:Long-Term Potentiation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D009187:Myelitis / Q000139:chemically induced / Q000276:immunology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides