Contributions
Abstract: P1146
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Objective: We studied the immunmodulatory effects of human immunoglobulins (Igs) applied intrathecally in the animal model of experimental autoimmune encephalomyelitis (EAE) in Lewis rats.
Background: Treatment with intravenous immunoglobulins (IVIg) has been proved effective only in a preventive concept for the animal model of multiple sclerosis (MS), the EAE. Clinical studies for relapsing remitting multiple sclerosis provide conflicting evidence on the therapeutic effect of intravenous immunoglobulins, so that their establishment as an immunomodulatory MS treatment has failed. However, the effect of immunoglobulins, which exert a wide spectrum of immunomodulatory actions, is dependent on a wide variety of factors such as the concentration given, the time-point and route of administration. Intrathecal drug administration is a widely applied alternate route of delivery in order to bypass the blood-brain barrier and achieve a direct effect in the cerebrospinal fluid and central nervous system.
Methods: Active EAE was induced by immunization with myelin basic protein (MBP) in Lewis rats followed by intrathecal application of 5 mg/kg, 10 mg/kg or 40 mg/kg Igs once daily at the beginning of clinical symptoms on days 11 and 13 p.i (post-immunisation). The clinical severity score was assessed daily until day 23 p.i.. Histological analyses of the spinal cord for demyelination, inflammatory infiltrates and complement activation, gene expression analyses of proinflammatory and anti-inflammatory cytokines as well as flow cytometric analyses of the peripheral lymph nodes and spleen were performed at the disease maximum (day 17 p.i.).
Results: Therapeutic treatment with 5 and 10mg/kg Igs applied intrathecally on days 11 and 13 p.i. significantly ameliorated clinical encephalomyelitis by reducing spinal cord demyelination. Further, histological analyses revealed a significantly lower degree of T cells and macrophages infiltrates compared with an increase of antiinflammatory cytokines such as IL-10 in the spinal cord at the disease maximum.
Conclusions: Intrathecal administration of human immunoglobulins in the rat model of autoimmune encephalomyelitis is a safe and effective immunmodulatory option. Further studies are required in order to investigate the safety and efficacy of intrathecal Ig application in human subjects with multiple sclerosis.
Disclosure:
K.P. received travel funding from Biogen Idec and Bayer Schering Pharma and speaker honoraria from Biogen Idec and Bayer Schering Pharma, not related to the manuscript.
H.B. has nothing to declare.
T.G. has nothing to declare.
J.M. has received travel funding from Biogen idec, not related to the manuscript.
B.A. received travel grants from Novartis, not related to this manuscript.
R.G. serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis, none related to this manuscript.
Abstract: P1146
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Objective: We studied the immunmodulatory effects of human immunoglobulins (Igs) applied intrathecally in the animal model of experimental autoimmune encephalomyelitis (EAE) in Lewis rats.
Background: Treatment with intravenous immunoglobulins (IVIg) has been proved effective only in a preventive concept for the animal model of multiple sclerosis (MS), the EAE. Clinical studies for relapsing remitting multiple sclerosis provide conflicting evidence on the therapeutic effect of intravenous immunoglobulins, so that their establishment as an immunomodulatory MS treatment has failed. However, the effect of immunoglobulins, which exert a wide spectrum of immunomodulatory actions, is dependent on a wide variety of factors such as the concentration given, the time-point and route of administration. Intrathecal drug administration is a widely applied alternate route of delivery in order to bypass the blood-brain barrier and achieve a direct effect in the cerebrospinal fluid and central nervous system.
Methods: Active EAE was induced by immunization with myelin basic protein (MBP) in Lewis rats followed by intrathecal application of 5 mg/kg, 10 mg/kg or 40 mg/kg Igs once daily at the beginning of clinical symptoms on days 11 and 13 p.i (post-immunisation). The clinical severity score was assessed daily until day 23 p.i.. Histological analyses of the spinal cord for demyelination, inflammatory infiltrates and complement activation, gene expression analyses of proinflammatory and anti-inflammatory cytokines as well as flow cytometric analyses of the peripheral lymph nodes and spleen were performed at the disease maximum (day 17 p.i.).
Results: Therapeutic treatment with 5 and 10mg/kg Igs applied intrathecally on days 11 and 13 p.i. significantly ameliorated clinical encephalomyelitis by reducing spinal cord demyelination. Further, histological analyses revealed a significantly lower degree of T cells and macrophages infiltrates compared with an increase of antiinflammatory cytokines such as IL-10 in the spinal cord at the disease maximum.
Conclusions: Intrathecal administration of human immunoglobulins in the rat model of autoimmune encephalomyelitis is a safe and effective immunmodulatory option. Further studies are required in order to investigate the safety and efficacy of intrathecal Ig application in human subjects with multiple sclerosis.
Disclosure:
K.P. received travel funding from Biogen Idec and Bayer Schering Pharma and speaker honoraria from Biogen Idec and Bayer Schering Pharma, not related to the manuscript.
H.B. has nothing to declare.
T.G. has nothing to declare.
J.M. has received travel funding from Biogen idec, not related to the manuscript.
B.A. received travel grants from Novartis, not related to this manuscript.
R.G. serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis, none related to this manuscript.