Protective effect of a germline, IL-17-neutralizing antibody in murine models of autoimmune inflammatory disease.

Monoclonal antibodies (mAbs) inhibiting cytokines have recently emerged as new drug modalities for the treatment of chronic inflammatory diseases. Interleukin-17 (IL-17) is a T-cell-derived central mediator of autoimmunity. Immunization with Qβ-IL-17, a virus-like particle based vaccine, has been shown to produce autoantibodies in mice and was effective in ameliorating disease symptoms in animal models of autoimmunity. To characterize autoantibodies induced by vaccination at the molecular level, we generated mouse mAbs specific for IL-17 and compared them to germline Ig sequences. The variable regions of a selected hypermutated high-affinity anti-IL-17 antibody differed in only three amino acid residues compared to the likely germline progenitor. An antibody, which was backmutated to germline, maintained a surprisingly high affinity (0.5 nM). The ability of the parental hypermutated antibody and the derived germline antibody to block inflammation was subsequently tested in murine models of multiple sclerosis (experimental autoimmune encephalomyelitis), arthritis (collagen-induced arthritis), and psoriasis (imiquimod-induced skin inflammation). Both antibodies were able to delay disease onset and significantly reduced disease severity. Thus, the mouse genome unexpectedly encodes for antibodies with the ability to functionally neutralize IL-17 in vivo.

Masking odour when regrouping rabbit does: Effect on aggression, stress and lesions.

Regrouping female rabbits (Oryctolagus cuniculus) in group housing systems is a common management practice in Swiss rabbit breeding which may, however, induce agonistic interactions resulting in social stress and severe lesions. On farms using artificial insemination, does are usually kept singly for 12 days after parturition to avoid pseudopregnancy and fighting for nests. The integration of new group members usually occurs after this isolation phase. This study was conducted with 128 gravid does of the Hycole hybrid, housed in pens covering a floor area of 5.7 m2 that was bedded with straw and furnished with elevated areas, hiding places and eight compartments with nest boxes. In the experiment, the fur of 16 groups of 8 does each was sprayed with either alcohol or vinegar to mask the pre-existing group odours, or with water (control groups) shortly before regrouping. Lesion scores, stress parameters (body temperature and blood glucose level) and behaviour were assessed before and after the isolation phase. Effects of treatment and time on all collected parameters were analysed using mixed models. On the second day after regrouping 43% of the does showed new lesions. In the first five days after regrouping, new lesions occurred in 60% of the does; 32% had severe lesions. After regrouping, more agonistic interactions were observed and body temperature and blood glucose levels were higher than before regrouping (P<0.001 each). Body temperature increased less in groups treated with vinegar compared to the other two treatments on the first day after regrouping (P=0.017). In all other parameters no influence of the treatment with alcohol or vinegar was found. These findings suggest that masking the group odours with alcohol or vinegar had little effect on lesions, stress and agonistic interactions. Therefore, alternative management procedures need to be developed to reduce lesions and stress caused by aggressive behaviour.