Contributions
Abstract: P1139
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Multiple scleroisis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Although primarily T and B cells are supposed to be actively involved in the inflammatory processes in CNS, growing evidence suggests antigen-presenting cells (APC) and especially dendritic cells (DC) as crucial players in the regulation of pro-inflammatory aspects in MS pathology. Teriflunomide is known to inhibit the mitochondrial enzyme dihydroorotat-dehydrogenase - the key-enzyme for pyrimidin-synthesis in activated T and B cells. Here we want to clarify, if teriflunomide targets APC and modulates APC versus T cells interaction in MS.
Methods: Different APC populations - monocytes (Mo), slanDC and plasmacytoid DC (pDC) - were immunomagnetically sorted and cultured in the presence or absence of different concentrations of teriflunomide with and without TLR4-stimulation. Changes in expression of surface activation and maturation markers were evaluated by FACS analysis. Supernatant was collected and analyzed regard cytokine release with ELISA. Additionally, impact of teriflunomid treated DC on polarisation of naïve CD4+ T cells was investigated.
Results: Teriflunomide treated Mo presented a dose depending decrease in release of pro-inflammatory cytokines including TNF-alpha, IL1-beta and IL-6. Expression of TNF-alpha and IL1-beta, but not IL-6 was impaired in slanDCs and pDCs. These data indicate distinct impact on pro-inflammatory capabilities of teriflunomide treatment. Teriflunomide pretreated DCs, presented decreased potential to induce naïve CD4+ T cells into interferon-gamma producing Th1 cells without impact on polarization IL-17 producing Th17 cells. Expression of surface activation and differentiation markers was not affected by teriflunomide in vitro treatment.
Conclusion: These data indicate, that modulation of APC and DC may play an additional role in mechanism of action and efficacy of teriflunomide therapy.
Disclosure:
K. Thomas received personal compensation for from Novartis, Biogen Idec and Roche for consulting service. Ziemssen received personal compensation from Biogen Idec, Bayer, Novartis, Sanofi, Teva, and Synthon for consulting services.
Ziemssen received additional financial support for research activities from Bayer, Biogen Idec, Novartis, Teva, and Sanofi Aventis.
I. Farhood has nothing to disclose.
Abstract: P1139
Type: Poster
Abstract Category: Therapy - disease modifying - 26 Immunomodulation/Immunosuppression
Background: Multiple scleroisis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Although primarily T and B cells are supposed to be actively involved in the inflammatory processes in CNS, growing evidence suggests antigen-presenting cells (APC) and especially dendritic cells (DC) as crucial players in the regulation of pro-inflammatory aspects in MS pathology. Teriflunomide is known to inhibit the mitochondrial enzyme dihydroorotat-dehydrogenase - the key-enzyme for pyrimidin-synthesis in activated T and B cells. Here we want to clarify, if teriflunomide targets APC and modulates APC versus T cells interaction in MS.
Methods: Different APC populations - monocytes (Mo), slanDC and plasmacytoid DC (pDC) - were immunomagnetically sorted and cultured in the presence or absence of different concentrations of teriflunomide with and without TLR4-stimulation. Changes in expression of surface activation and maturation markers were evaluated by FACS analysis. Supernatant was collected and analyzed regard cytokine release with ELISA. Additionally, impact of teriflunomid treated DC on polarisation of naïve CD4+ T cells was investigated.
Results: Teriflunomide treated Mo presented a dose depending decrease in release of pro-inflammatory cytokines including TNF-alpha, IL1-beta and IL-6. Expression of TNF-alpha and IL1-beta, but not IL-6 was impaired in slanDCs and pDCs. These data indicate distinct impact on pro-inflammatory capabilities of teriflunomide treatment. Teriflunomide pretreated DCs, presented decreased potential to induce naïve CD4+ T cells into interferon-gamma producing Th1 cells without impact on polarization IL-17 producing Th17 cells. Expression of surface activation and differentiation markers was not affected by teriflunomide in vitro treatment.
Conclusion: These data indicate, that modulation of APC and DC may play an additional role in mechanism of action and efficacy of teriflunomide therapy.
Disclosure:
K. Thomas received personal compensation for from Novartis, Biogen Idec and Roche for consulting service. Ziemssen received personal compensation from Biogen Idec, Bayer, Novartis, Sanofi, Teva, and Synthon for consulting services.
Ziemssen received additional financial support for research activities from Bayer, Biogen Idec, Novartis, Teva, and Sanofi Aventis.
I. Farhood has nothing to disclose.