Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation.
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.
Galle
Pia
P
Department of Clinical Immunology, Rigshospitalet, National University Hospital, Copenhagen, Denmark.
Jensen
Lene
L
Andersson
Christina
C
Cuzzocrea
Salvatore
S
Di Paola
Rosanna
R
Nicoletti
Ferdinando
F
Svenson
Morten
M
Bendtzen
Klaus
K
Thomsen
Allan R
AR
Hansen
Morten B
MB
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
D001323:Autoantibodies; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha