Intraperitoneal and subcutaneous injections of the TLR9 agonist ODN 1668 in rats: Brain inflammatory responses are related to peripheral IL-6 rather than interferons

• Published in: Journal of neuroimmunology Vol. 277; no. 1; pp. 105 - 117
• Main Authors: Damm, J, Wiegand, F, Harden, L.M, Wenisch, S, Gerstberger, R, Rummel, C, Roth, J
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-12-2014
• Subjects: Allergy and Immunology; Animals; Cytokines; Dinoprostone - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking - drug effects; Drug Administration Routes; Eating - drug effects; Encephalitis - chemically induced; Encephalitis - metabolism; Fever; Gene Expression Regulation - drug effects; Immune-to-brain signaling; Inflammatory transcription factors; Injections, Intraperitoneal; Injections, Subcutaneous; Interferons; Interferons - genetics; Interferons - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Male; Motor Activity - drug effects; Neurology; Oligodeoxyribonucleotides - toxicity; Rats; Rats, Wistar; Time Factors; Toll-Like Receptor 9 - agonists; Toll-Like Receptor 9 - chemistry; Toll-like receptors; suppressor of cytokine signaling 3; IHC; cyclooxygenase-2; OVLT; TNF; microsomal prostaglandin E synthase; enzyme-linked immuno-sorbent assay; prostaglandin E2; RT-PCR; ODN; Toll-like receptor; PBS; IL; NFκB; Cytokines; circumventricular organs; CVOs; standard error; AP; IκBα; Inflammatory transcription factors; T abd; abdominal temperature; ELISA; pathogen associated molecular pattern; oligodeoxynucleotides; COX-2; organum vasculosum laminae terminalis; vWF; cytosine–phosphate–guanosine dinucleotides; Interferons; nuclear factor kappa B; inhibitor kappa B alpha; area postrema; IFN; SOCS3; SE; von Willebrand factor; NF-IL6; Toll-like receptors; CpG; immunohistochemistry; TLR; interleukin; PGE2; Immune-to-brain signaling; nuclear factor IL6; STAT3; signal transducer and activator of transcription 3; interferon; Fever; PAMP; tumor necrosis factor; phosphate buffered saline; mPGES; real time polymerase chain reaction; Tabd
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2014.10.007

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.