TY - JOUR
T1 - Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation
AU - Galle, Pia
AU - Jensen, Lene
AU - Andersson, Christina
AU - Cuzzocrea, Salvatore
AU - Di Paola, Rosanna
AU - Nicoletti, Ferdinando
AU - Svenson, Morten
AU - Bendtzen, Klaus
AU - Thomsen, Allan Randrup
AU - Hansen, Morten B
N1 - Keywords: Animals; Arthritis, Experimental; Autoantibodies; Encephalomyelitis, Autoimmune, Experimental; Interleukin-6; Lipopolysaccharides; Mice; Mice, Inbred Strains; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha; Vaccination
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
KW - Animals
KW - Arthritis, Experimental
KW - Autoantibodies
KW - Encephalomyelitis, Autoimmune, Experimental
KW - Interleukin-6
KW - Lipopolysaccharides
KW - Mice
KW - Mice, Inbred Strains
KW - Serum Amyloid A Protein
KW - Tumor Necrosis Factor-alpha
KW - Vaccination
U2 - 10.1016/j.intimp.2007.08.026
DO - 10.1016/j.intimp.2007.08.026
M3 - Journal article
C2 - 17996680
SN - 1567-5769
VL - 7
SP - 1704
EP - 1713
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 13
ER -