title: Intraperitoneal and subcutaneous injections of the TLR9 agonist ODN 1668 in rats: brain inflammatory responses are related to peripheral IL-6 rather than interferons.
abstract: Subcutaneous or intraperitoneal administration of Toll-like receptor (TLR)-9 agonist, ODN 1668 caused moderate fever and anorexia. In comparison to stimulation of other intracellular TLRs, activation of TLR9 did not result in pronounced peripheral induction of interferons, but rather induced interleukin-6. Expression of cytokines (TNFα, IL-1β) and inducible forms of enzymes for prostaglandin E2 synthesis occurred in the brain, in conjunction with a moderate activation of the transcription factors STAT3 and NF-IL6 in brain endothelial cells. The lack of a septic-like state in ODN 1668-treated rats reinforces the therapeutic value of this drug.
authors.affiliation: Institute of Veterinary-Physiology and -Biochemistry, Justus-Liebig-University of Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Damm
authors.affiliation: Institute of Veterinary-Physiology and -Biochemistry, Justus-Liebig-University of Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Wiegand
authors.affiliation: Institute of Veterinary-Physiology and -Biochemistry, Justus-Liebig-University of Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany; Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, South Africa.
authors.forename: L M
authors.initials: LM
authors.lastname: Harden
authors.affiliation: Institute of Veterinary-Anatomy, Justus-Liebig-University of Giessen, Frankfurter Strasse 98, D-35392 Giessen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Wenisch
authors.affiliation: Institute of Veterinary-Physiology and -Biochemistry, Justus-Liebig-University of Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Gerstberger
authors.affiliation: Institute of Veterinary-Physiology and -Biochemistry, Justus-Liebig-University of Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rummel
authors.affiliation: Institute of Veterinary-Physiology and -Biochemistry, Justus-Liebig-University of Giessen, Frankfurter Strasse 100, D-35392 Giessen, Germany. Electronic address: Joachim.Roth@vetmed.uni-giessen.de.
authors.forename: J
authors.initials: J
authors.lastname: Roth
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004333:Drug Administration Routes; D004435:Eating / Q000187:drug effects; D004660:Encephalitis / Q000139:chemically induced* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009838:Oligodeoxyribonucleotides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000737:chemistry*
chemical_list: D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D007372:Interferons; D015232:Dinoprostone
keywords: Cytokines; Fever; Immune-to-brain signaling; Inflammatory transcription factors; Interferons; Toll-like receptors