title: Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation.
abstract: IL-6 is involved in inflammation and a therapeutic target. 0.1% of Danish blood donors have nanomolar plasma concentrations of polyclonal, picomolar affinity and in vitro as well as in vivo neutralizing IgG autoantibodies to IL-6 (aAb-IL-6). Such donors are assumed to be severely IL-6 deficient; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental allergic encephalitis. Furthermore, aAb-IL-6 carrying mice displayed increased plasma TNFalpha concentrations upon challenge with LPS. Taken together, induction of IL-6 autoantibodies was possible in different mouse strains. The autoantibodies influenced experimental inflammation. This immunotherapeutic principle might be a viable alternative in immune competent humans suffering from disorders driven by IL-6.
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, National University Hospital, Copenhagen, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Galle
authors.forename: Lene
authors.initials: L
authors.lastname: Jensen
authors.forename: Christina
authors.initials: C
authors.lastname: Andersson
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Morten
authors.initials: M
authors.lastname: Svenson
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Allan R
authors.initials: AR
authors.lastname: Thomsen
authors.forename: Morten B
authors.initials: MB
authors.lastname: Hansen
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D001323:Autoantibodies / Q000096:biosynthesis*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D000685:Serum Amyloid A Protein / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014611:Vaccination
chemical_list: D001323:Autoantibodies; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha