Vaccination with IL-6 analogues induces autoantibodies to IL-6 and influences experimentally induced inflammation

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 -