Messung der murinen anti-humanen Antikörperreaktion sowie Beurteilung der allgemeinen Aktivität und Kognition von gesunden adulten Mäusen nach Behandlung mit intravenösen Immunglobulinen

Präparate aus intravenösen Immunglobulinen (IVIG) sind Blutprodukte, welche bereits in der klinischen Therapie verschiedener entzündlicher, Autoimmun- oder Immundefizienzerkrankungen sowie insbesondere im Bereich der Therapieforschung von neurodegenerativen Erkrankungen wie unter anderem der Alzheim...

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Bibliographische Detailangaben
1. Verfasser: Fülber, Isabelle
Beteiligte: Dodel, Richard (Dr. med) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Deutsch
Veröffentlicht: Philipps-Universität Marburg 2016
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Intravenous Immunglobulins (IVIG) are blood products of pooled human serum, which is used in different inflammatory, autoimmune- or immunodeficiency disorders, especially in experimental research of neurodegenerative diseases like Alzheimer’s disease. The detailed mode of action is not well known, yet. Therefore preclinical ratings of therapeutic efficiency from IVIG in animal models are needed to understand the mode of action of IVIG in vivo. To gain knowledge about this mode of action from IVIG in vivo, it is essential to capture the murine reaction of human anti-bodies (MAHA-reaction) in the animal model. With this knowledge it is possible to subsequently draw conclusions and deduce on therapeutic efficiency and to start biological and tests for cognition processes in vivo. Based on the knowledge that human antibodies are foreign antigens to the murine immune system, it is reasonable to assume that an immunomodulatory reaction is caused with the generation of specific antibodies in mice, which were injected with IVIG. Potentially, there can be a neutralizing effect caused by forming antigen-antibody-complexes. Bound in complexes, the antibodies might not be able to take part in the reaction that is examined. Furthermore, it is possible that the immunological reaction changes the behavior of the tested animals, which can be misinterpreted as a therapeutic reaction or divert this therapeutic reaction. In this thesis C57/B6J mice were injected weekly with 400µg IVIG intraperitoneal over a period of 12 weeks. There was a significant MAHA-reaction after week 9 without any change in basic behavior like exploratory behavior or fear as well as cognition. It has been demonstrated that a treatment of wild type mice with IVIG over a period of 10 weeks causes a significant MAHA-reaction but does not induce any changes in basic behavior. Therefore, it is possible to draw conclusions about the pharmacological and immunological activities as well as therapeutic efficiency of IVIG in animal models for periods of an examination over a duration comparable to the one evaluated. During this period there is no measurable interaction or neutralization of therapeutic effects caused by a MAHA-reaction.