Interleukin-6 is a candidate molecule that transmits inflammatory information to the CNS.
Peripheral inflammation induces reactions within the CNS such as central sensitization, which is involved in the mechanism of inflammatory hyperalgesia. However, the precise mechanism of inflammatory signal transmission from the peripheral inflammatory site to the CNS is not clear. We studied the role of circulating interleukin (IL)-6 as a messenger of inflammatory information from the periphery to the CNS. In the rat model of inflammatory hyperalgesia induced by carrageenan, levels of IL-6 but not IL-1beta or tumor necrosis factor alpha (TNFalpha) were significantly elevated in the circulating blood 3 h after an injection of carrageenan. In addition, injecting carrageenan into the hind paw evoked thermal hyperalgesia and the release of prostaglandin E(2) (PGE(2)) from isolated blood vessels of the CNS ex vivo, as well as the induction of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in vascular endothelial cells of the CNS. A prior i.p. injection of IL-6 antiserum (IL-6AS) abolished or attenuated these responses. The present results suggested that circulating IL-6 could act as a messenger of inflammatory information from peripheral inflammatory sites to the CNS and as the afferent circulating signal to the CNS to produce prostaglandins in the vascular endothelial cells of the CNS through a COX-2 dependent pathway.
Oka
Y
Y
Department of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Ibuki
T
T
Matsumura
K
K
Namba
M
M
Yamazaki
Y
Y
Poole
S
S
Tanaka
Y
Y
Kobayashi
S
S
D000344:Afferent Pathways / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002490:Central Nervous System / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000097:blood / Q000378:metabolism; D015232:Dinoprostone / Q000097:blood / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005528:Foot / Q000294:innervation / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000009:adverse effects; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008297:Male; D010525:Peripheral Nerves / Q000276:immunology*; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000097:blood / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000276:immunology* / Q000503:physiopathology; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D000906:Antibodies; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D018836:Inflammation Mediators; D015850:Interleukin-6; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C494088:Stat3 protein, rat; C497818:Ptges protein, rat