Author(s): van Westerloo DJ, Giebelen IA, Florquin S, Bruno MJ, Larosa GJ, et al.
Background & aims:The nervous system, through the vagus nerve, controls inflammation by decreasing the release of tumor necrosis factor-alpha from endotoxin stimulated macrophages. This anti-inflammatory effect is mediated by an interaction of acetylcholine, the principal neurotransmitter of the vagus nerve, with macrophage cholinergic nicotinic receptors expressing the alpha7 subunit.
Methods:To determine the role of this "nicotinic anti-inflammatory pathway" in experimental pancreatitis, we induced pancreatitis in mice by 12 hourly intraperitoneal injections of cerulein. Pancreatitis was preceded by unilateral left cervical vagotomy or pretreatment with the nicotinic receptor antagonist mecamylamine or by pretreatment with the selective alpha7 nicotinic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21).
Results:Vagotomy or pretreatment with mecamylamine resulted in an enhanced severity of pancreatitis, as reflected by histology, edema, plasma hydrolases, and interleukin-6 levels. Furthermore, the number of neutrophils migrated to the pancreas was increased in these mice, as shown by myeloperoxidase content and intrapancreatic staining of neutrophils. Conversely, GTS-21 pretreatment strongly decreased the severity of pancreatitis. Pancreatitis-associated pulmonary inflammation was independent of the integrity of the vagus nerve and nicotinic receptors.
Conclusions:This study provides the first evidence for a therapeutic potential of the vagus nerve and the "nicotinic anti-inflammatory pathway" in attenuating inflammation and injury during experimental pancreatitis.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/16697744
Author(s): McDougall AJ, McLeod JG
Author(s): Nortvedt MW, Riise T, Frugård J, Mohn J, Bakke A, et al.
Author(s): Wiesel PH, Norton C, Glickman S, Kamm MA
Author(s): Flachenecker P, Rufer A, Bihler I, Hippel C, Reiners K, et al.
Author(s): Keselbrener L, Akselrod S, Ahiron A, Eldar M, Barak Y, et al.
Author(s): Hale LA, Nukada H, Du Plessis LJ, Peebles KC
Author(s): Flachenecker P, Reiners K, Krauser M, Wolf A, Toyka KV
Author(s): Watkins LR, Maier SF
Author(s): Zoukos Y, Kidd D, Woodroofe MN, Kendall BE, Thompson AJ, et al.
Author(s): Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES
Author(s): Hasko G, Elenkov IJ, Kvetan V, Vizi ES
Author(s): Sternberg Z
Author(s): Jager A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK
Author(s): Cosentino M, Marino F
Author(s): Grisanti LA, Woster AP, Dahlman J, Sauter ER, Combs CK, et al.
Author(s): Lorton D, Lubahn C, Bellinger DL
Author(s): Tracey KJ
Author(s): Nicolussi EM, Huck S, Lassmann H, Bradl M
Author(s): Gage JR, Fonarow G, Hamilton M, Widawski M, Martinez-Maza O, et al.
Author(s): Sternberg Z, Leung C, Sternberg D, Li F, Karmon Y, et al.
Author(s): Berne-Fromell K, Fromell H, Lundkvist S, Lundkvist P
Author(s): Szramka M, Harriss L, Ninnio D, Windebank E, Brack J, et al.
Author(s): Neuhaus O, Stüve O, Zamvil SS, Hartung HP
Author(s): Birnbaum G, Cree B, Altafullah I, Zinser M, Reder AT
Author(s): Bhat R, Axtell R, Mitra A, Miranda M, Lock C, et al.
Author(s): Suzdak PD, Gianutsos G
Author(s): Yoshimura R, Ueda N, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, et al.
Author(s): Kubota T, Hirota K, Yoshida H, Takahashi S, Anzawa N, et al.
Author(s): Brawek B, Löffler M, Dooley DJ, Weyerbrock A, Feuerstein TJ
Author(s): de Saint Hilaire Z, Orosco M, Rouch C, Blanc G, Nicolaidis S
Author(s): Nader ND, Ignatowski TA, Kurek CJ, Knight PR, Spengler RN
Author(s): Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, et al.
Author(s): Kox M, van Velzen JF, Pompe JC, Hoedemaekers CW, van der Hoeven JG, et al.
Author(s): Giebelen IA, van Westerloo DJ, LaRosa GJ, de Vos AF, van der Poll T
Author(s): Ku YT, Montgomery LD, Lee HC, Luna B, Webbon BW
Author(s): Kinugasa H, Hirayanagi K