title: Interleukin-6 in combination with its soluble IL-6 receptor sensitises rat skin nociceptors to heat, in vivo.
abstract: Interleukin-6 (IL-6) contributes to increased pain and hyperalgesia in inflamed tissue. We have investigated the effects of IL-6, alone or in combination with its soluble receptor (sIL-6R), on the sensitivity of nociceptors to noxious heat, using dermal microdialysis. Plasmapheresis membranes were inserted into the abdominal skin of adult male Wistar rats (n=46) and perfused with modified Ringer solution. After three control samples (20 min each), the skin area above the membrane was heated to 48 degrees C for 20 min. The stimulation was followed by two washout samples. The calcitonin gene-related peptide (CGRP) content of the dialysate was measured with an enzyme immunoassay. Heat stimulation provoked a significant CGRP increase in the dialysate. Intradermal application of IL-6 (200 ng ml-1) did not significantly alter heat-induced CGRP release. However, a significant sensitisation of the heat-induced CGRP release was observed when sIL-6R (25 ng ml-1) was applied, either alone or in combination with IL-6. Neutralisation of endogenous IL-6 with a sheep anti-rat IL-6 serum did not alter heat-induced CGRP release, but abolished the sIL-6R-mediated sensitising effect. We show that IL-6 in combination with its soluble receptor can sensitise nociceptors to heat and provide evidence for the constitutive expression of the signalling molecule gp130, but not of the IL-6-membrane-bound (specific) receptor, in nociceptors.
authors.affiliation: Institut für Physiologie und Experimentelle Pathophysiologie, Universitätsstrasse 17, Erlangen, Germany.
authors.forename: Otilia
authors.initials: O
authors.lastname: Obreja
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
authors.forename: Stephen
authors.initials: S
authors.lastname: Poole
authors.forename: Michaela
authors.initials: M
authors.lastname: Kress
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D050822:Cytokine Receptor gp130; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D017551:Microdialysis; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; C494201:Il6st protein, rat; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011506:Proteins; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130; D015740:Calcitonin Gene-Related Peptide