title: Reflex control of inflammation by the splanchnic anti-inflammatory pathway is sustained and independent of anesthesia.
abstract: Following an immune challenge, there is two-way communication between the nervous and immune systems. It is proposed that a neural reflex--the inflammatory reflex--regulates the plasma levels of the key proinflammatory cytokine TNF-α, and that its efferent pathway is in the splanchnic sympathetic nerves. The evidence for this reflex is based on experiments on anesthetized animals, but anesthesia itself suppresses inflammation, confounding interpretation. Here, we show that previous section of the splanchnic nerves strongly enhances the levels of plasma TNF-α in conscious rats 90 min after they received intravenous LPS (60 μg/kg). The same reflex mechanism, therefore, applies in conscious as in anesthetized animals. In anesthetized rats, we then determined the longer-term effects of splanchnic nerve section on responses to LPS (60 μg/kg iv). We confirmed that prior splanchnic nerve section enhanced the early (90 min) peak in plasma TNF-α and found that it reduced the 90-min peak of the anti-inflammatory cytokine IL-10; both subsequently fell to low levels in all animals. Splanchnic nerve section also enhanced the delayed rise in two key proinflammatory cytokines IL-6 and interferon γ. That enhancement was undiminished after 6 h, when other measured cytokines had subsided. Finally, LPS treatment caused hypotensive shock in rats with cut splanchnic nerves but not in sham-operated animals. These findings demonstrate that reflex activation of the splanchnic anti-inflammatory pathway has a powerful and sustained restraining influence on inflammatory processes.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia;
authors.forename: Davide
authors.initials: D
authors.lastname: Martelli
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia;
authors.forename: Song T
authors.initials: ST
authors.lastname: Yao
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia; Facultad de Medicina, Universidad de los Andes, Bogota, Colombia;
authors.forename: Julian
authors.initials: J
authors.lastname: Mancera
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia; Department of Physiology, University of Melbourne, Parkville, Victoria, Australia; and.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McKinley
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia rmca@florey.edu.au.
authors.forename: Robin M
authors.initials: RM
authors.lastname: McAllen
mesh_terms: D000758:Anesthesia; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013153:Splanchnic Nerves / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D003345:Corticosterone
keywords: lipopolysaccharide; sympathetic nervous system; tumor necrosis factor-α