Lühder, Fred

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","2"],["dc.bibliographiccitation.volume","192"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Gold, Ralf"],["dc.date.accessioned","2018-11-07T10:48:55Z"],["dc.date.available","2018-11-07T10:48:55Z"],["dc.date.issued","2007"],["dc.identifier.doi","10.1016/j.jneuroim.2007.10.011"],["dc.identifier.isi","000252163200001"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48312"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-5728"],["dc.title","Many roads lead to Rome: Heterogeneity among encephalitogenic T cell clones"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","397"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Experimental Neurology"],["dc.bibliographiccitation.lastpage","406"],["dc.bibliographiccitation.volume","211"],["dc.contributor.author","Linker, Ralf A."],["dc.contributor.author","Weller, Charlotte"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Mohr, Alexander"],["dc.contributor.author","Schmidt, Jens"],["dc.contributor.author","Knauth, Michael"],["dc.contributor.author","Metselaar, Josbert M."],["dc.contributor.author","Gold, Ralf"],["dc.date.accessioned","2018-11-07T11:14:26Z"],["dc.date.available","2018-11-07T11:14:26Z"],["dc.date.issued","2008"],["dc.description.abstract","Liposomal encapsulation leads to enhanced efficacy of glucocorticosteroids (GS) in treatment of autoimmune diseases. Here we compare liposomal prednisolone (PL) to liposomal methylprednisolone (MPL) in chronic-relapsing myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), a model closely reflecting aspects of multiple sclerosis (MS). At the maximum of the first relapse, a single dose of PL or MPL was applied at 10 mg/kg or at 4 mg/kg and compared to classical methylprednisolone (MP) pulse therapy. PL at 10 mg/kg was superior to free MP with long-term efficacy and a sustained protection even during the second and third relapse. At the same time, in vivo magnetic resonance imaging of rat brains revealed a significant reduction of T2-lesions after PL application. Comparison of PL and MPL at 10 mg/kg disclosed superior effects for MPL with an enhanced reduction of inflammatory infiltration as well as preservation of myelin and axons. Dose titration experiments underscored a dose-dependent efficacy of liposomal GS with a sustained efficacy especially of the higher dosage. In histological analyses, PL10 was superior in reducing macrophage and T cell infiltration as well as demyelination and axonal loss while the lower dosages were still at least as effective as free MP. FACS analyses revealed an effect of liposome formulations on T cell numbers, the CD4/CD8 ratio, frequencies of regulatory T cells and adhesion molecule expression. In summary, liposomal GS and especially methylprednisolone formulations display an enhanced efficacy not only in acute inflammatory, but also in chronic demyelinating models of MS and confer long-term protection from relapses. These findings lay the groundwork for applying liposomal GS in clinical MS trials in the near future. (c) 2008 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.expneurol.2008.02.005"],["dc.identifier.isi","000256272800012"],["dc.identifier.pmid","18394606"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54122"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","0014-4886"],["dc.title","Liposomal glucocorticosteroids in treatment of chronic autoimmune demyelination: Long-term protective effects and enhanced efficacy of methylprednisolone formulations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","7"],["dc.bibliographiccitation.volume","217"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Lee, De-Hyung"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Stegbauer, Johannes"],["dc.contributor.author","Linker, Ralf Andreas"],["dc.date.accessioned","2018-11-07T11:21:07Z"],["dc.date.available","2018-11-07T11:21:07Z"],["dc.date.issued","2009"],["dc.description.abstract","In the recent years, it has become increasingly clear that the immune response is also influenced by mediators which were first discovered as regulators in the nervous or also cardiovascular system. Here, small peptide hormones may play an important role. Kinins like bradykinins act on the endothelium and play a role for trafficking of lymphocytes over the blood-brain barrier. Neuropeptides like vasoactive intestinal peptide or neuropeptide Y also directly act on T cells and favour the differentiation of Th2 cells or regulatory T cell populations. Recently, the renin-angiotensin system (RAS) came into the focus of interest. Inhibition of the RAS at different levels may influence autoimmune responses and involve T cells as well as antigen-presenting cells, probably via different signalling pathways. Inhibitors of angiotensin converting enzyme and antagonists of the angiotensin I receptors are used in the treatment of hypertension, kidney disease or stroke by millions of people worldwide. These inexpensive and safe pharmaceuticals may also represent an interesting and innovative approach for the (combination) treatment of autoimmune diseases like multiple sclerosis. (C) 2009 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jneuroim.2009.08.008"],["dc.identifier.isi","000272896700001"],["dc.identifier.pmid","19748684"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55698"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-5728"],["dc.title","Small but powerful: Short peptide hormones and their role in autoimmune inflammation"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Clinical Immunology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Schilling, S."],["dc.contributor.author","Goelz, S."],["dc.contributor.author","Linker, Ralf Andreas"],["dc.contributor.author","Luhder, F."],["dc.contributor.author","Gold, Ralf"],["dc.date.accessioned","2018-11-07T08:36:16Z"],["dc.date.available","2018-11-07T08:36:16Z"],["dc.date.issued","2005"],["dc.format.extent","S88"],["dc.identifier.isi","000229104400244"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18269"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.publisher.place","San diego"],["dc.relation.conference","5th Annual Meeting of the Federation-of-Clinical-Immunology-Society"],["dc.relation.eventlocation","Boston, MA"],["dc.relation.issn","1521-6616"],["dc.title","Fumarate therapy ameloriates chronic experimental autoimmune encephalomyelitis (EAE)."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2517"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2530"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Cotte, S."],["dc.contributor.author","von Ahsen, Nicolas"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Huber, B."],["dc.contributor.author","Winkelmann, Alexander"],["dc.contributor.author","Zettl, Uwe K."],["dc.contributor.author","Starck, Michaela"],["dc.contributor.author","Koenig, N."],["dc.contributor.author","Tellez, N."],["dc.contributor.author","Doerr, J."],["dc.contributor.author","Paul, Friedemann"],["dc.contributor.author","Zipp, Frauke"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Koepsell, Hermann"],["dc.contributor.author","Pannek, H."],["dc.contributor.author","Montalban, Xavier"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Chan, A."],["dc.date.accessioned","2018-11-07T11:24:34Z"],["dc.date.available","2018-11-07T11:24:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Escalation therapy with mitoxantrone (MX) in highly active multiple sclerosis is limited by partially dose-dependent side-effects. Predictors of therapeutic response may result in individualized risk stratification and MX dosing. ATP-binding cassette-transporters ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active cellular MX efflux. Here, we investigated the role of ABC-gene single nucleotide polymorphisms (SNPs) for clinical MX response, corroborated by experimental in vitro and in vivo data. Frequencies of ABCB1 2677GT, 3435CT and five ABCG2-SNPs were analysed in 832 multiple sclerosis patients (Germany, Spain) and 264 healthy donors. Using a flow-cytometry-based in vitro assay, MX efflux in leukocytes from individuals with variant alleles in both ABC-genes (designated genotype ABCB1/ABCG2-L(ow), 22.2 of patients) was 37.7 lower than from individuals homozygous for common alleles (ABCB1/ABCG2-H(igh), P 0.05, 14.8 of patients), resulting in genotype-dependent MX accumulation and cell death. Addition of glucocorticosteroids (GCs) inhibited MX efflux in vitro. ABC-transporters were highly expressed in leukocyte subsets, glial and neuronal cells as well as myocardium, i.e. cells/tissues potentially affected by MX therapy. In vivo significance was further corroborated in experimental autoimmune encephalomyelitis in Abcg2(/) animals. Using a MX dose titrated to be ineffective in wild-type animals, disease course and histopathology in Abcg2(/) mice were strongly ameliorated. Retrospective clinical analysis in MX monotherapy patients (n 155) used expanded disability status scale, relapse rate and multiple sclerosis functional composite as major outcome parameters. The clinical response rate [overall 121 of 155 patients (78.1)] increased significantly with genotypes associated with decreasing ABCB1/ABCG2-function [ABCB1/ABCG2-H 15/24 (62.5) responders, ABCB1/ABCG2-I(ntermediate) 78/98 (79.6), ABCB1/ABCG2-L 28/33 (84.8), exact Cochran-Armitage test P 0.039]. The odds ratio for response was 1.9 (95 CI 1.03.5) with each increase in ABCB1/ABCG2 score (from ABCB1/ABCG2-H to I-, and I to L). In 36 patients with severe cardiac or haematological side effects no statistically relevant difference in genotype frequency was observed. However, one patient with biopsy proven cardiomyopathy only after 24 mg/m(2) MX exhibited a rare genotype with variant, partly homozygous alleles in 3 ABC-transporter genes. In conclusion, SNPs in ABC-transporter genes may serve as pharmacogenetic markers associated with clinical response to MX therapy in multiple sclerosis. Combined MX/GC-treatment warrants further investigation."],["dc.description.sponsorship","Merck Serono, Germany"],["dc.identifier.doi","10.1093/brain/awp164"],["dc.identifier.isi","000269963600021"],["dc.identifier.pmid","19605531"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6073"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56436"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e4643"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Gogishvili, Tea"],["dc.contributor.author","Langenhorst, Daniela"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Elias, Fernando"],["dc.contributor.author","Elflein, Karin"],["dc.contributor.author","Dennehy, Kevin M."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Huenig, Thomas"],["dc.date.accessioned","2018-11-07T08:32:35Z"],["dc.date.available","2018-11-07T08:32:35Z"],["dc.date.issued","2009"],["dc.description.abstract","Superagonistic CD28-specific monoclonal antibodies (CD28SA) are highly effective activators of regulatory T-cells (Treg cells) in rats, but a first-in-man trial of the human CD28SA TGN1412 resulted in an unexpected cytokine release syndrome. Using a novel mouse anti-mouse CD28SA, we re-investigate the relationship between Treg activation and systemic cytokine release. Treg activation by CD28SA was highly efficient but depended on paracrine IL-2 from CD28SA-stimulated conventional T-cells. Systemic cytokine levels were innocuous, but depletion of Treg cells prior to CD28SA stimulation led to systemic release of proinflammatory cytokines, indicating that in rodents, Treg cells effectively suppress the inflammatory response. Since the human volunteers of the TGN1412 study were not protected by this mechanism, we also tested whether corticosteroid prophylaxis would be compatible with CD28SA induced Treg activation. We show that neither the expansion nor the functional activation of Treg cells is affected by high-dose dexamethasone sufficient to control systemic cytokine release. Our findings warn that preclinical testing of activating biologicals in rodents may miss cytokine release syndromes due to the rapid and efficacious response of the rodent Treg compartment, and suggest that polyclonal Treg activation is feasible in the presence of antiphlogistic corticosteroid prophylaxis."],["dc.identifier.doi","10.1371/journal.pone.0004643"],["dc.identifier.isi","000265487800023"],["dc.identifier.pmid","19247496"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5818"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17376"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Rapid Regulatory T-Cell Response Prevents Cytokine Storm in CD28 Superagonist Treated Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","43"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Critical Reviews in Immunology"],["dc.bibliographiccitation.lastpage","68"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Linker, Ralf A."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T08:34:17Z"],["dc.date.available","2018-11-07T08:34:17Z"],["dc.date.issued","2009"],["dc.description.abstract","In the nervous system, neurotrophic factors play a role during development, especially for the differentiation of neuronal and glial cells. Moreover, they promote cell survival of neurons, axons, and oligodendrocytes, as well as their precursors, in vitro and in lesional paradigms. In recent years, several functions of neurotrophic factors outside the nervous system have been described, with a special focus on the immune system as well as on models of autoimmune demyelination, such as experimental autoimmune encephalomyelitis (EAE). In the family of neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were investigated. NGF may influence B-cell as well as T-cell function and particularly plays a role in macrophage migration into inflamed lesions. BDNF is produced by several immune-cell subtypes in vitro and also in multiple sclerosis (MS) plaques. This observation gave rise to the concept of neuroprotective autoimmunity, implying that immune-cell infiltration in the nervous system may not only be detrimental but may also play a beneficial role, for example, through the production of neurotrophic factors. In the family of neurotrophic cytokines, ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) share some common protective roles in axons and oligodendrocytes. In EAE, endogenous CNTF targets myelin, oligodendroglial cells, and axons. In contrast, LIF exerts protective functions on oligodendrocytes in some models but is also able to interact with the immune response and may modulate T-cell, monocyte and neutrophil functions. In summary, neurotrophic factors have distinct roles in the immune system during autoimmunity and may modulate immune responses as well as the susceptibility of the target tissue."],["dc.identifier.isi","000265560700002"],["dc.identifier.pmid","19348610"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17776"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Begell House Inc"],["dc.relation.issn","1040-8401"],["dc.title","Function of Neurotrophic Factors Beyond the Nervous System: Inflammation and Autoimmune Demyelination"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2248"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","2263"],["dc.bibliographiccitation.volume","133"],["dc.contributor.author","Linker, Ralf A."],["dc.contributor.author","Lee, De-Hyung"],["dc.contributor.author","Demir, Seray"],["dc.contributor.author","Wiese, Stefan"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Siglienti, Ines"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Neumann, Harald"],["dc.contributor.author","Sendtner, Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Gold, Ralf"],["dc.date.accessioned","2018-11-07T08:40:38Z"],["dc.date.available","2018-11-07T08:40:38Z"],["dc.date.issued","2010"],["dc.description.abstract","Brain-derived neurotrophic factor plays a key role in neuronal and axonal survival. Brain-derived neurotrophic factor is expressed in the immune cells in lesions of experimental autoimmune encephalomyelitis and multiple sclerosis, thus potentially mediating neuroprotective effects. We investigated the functional role of brain-derived neurotrophic factor in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Mice deficient for brain-derived neurotrophic factor in immune cells displayed an attenuated immune response in the acute phase of experimental autoimmune encephalomyelitis, but progressive disability with enhanced axonal loss in the chronic phase of the disease. In mice deficient for central nervous system-derived brain-derived neurotrophic factor via glial fibrillary acidic protein-crescentin-mediated deletion, a more severe course of experimental autoimmune encephalomyelitis and an overall increased axonal loss was observed. In a lentiviral approach, injection of brain-derived neurotrophic factor-overexpressing T cells led to a less severe course of experimental autoimmune encephalomyelitis and direct axonal protection. Our data imply a functional role of brain-derived neurotrophic factor in autoimmune demyelination by mediating axon protection."],["dc.identifier.doi","10.1093/brain/awq179"],["dc.identifier.isi","000280982700010"],["dc.identifier.pmid","20826430"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6203"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19277"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","202"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","203"],["dc.bibliographiccitation.volume","275"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Linker, Ralf"],["dc.contributor.author","Lee, De-hyung"],["dc.contributor.author","Reichardt, Holger"],["dc.contributor.author","Bommhardt, Ursula"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T09:33:36Z"],["dc.date.available","2018-11-07T09:33:36Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1016/j.jneuroim.2014.08.544"],["dc.identifier.isi","000345192100533"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32000"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","12th International Congress of Neuroimmunology (ISNI)"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.title","Critical role of thymocyte-derived brain-derived neurotrophic factor in T cell maturation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Wiener klinische Wochenschrift"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Wuest, S."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Reichardt, M."],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T11:12:50Z"],["dc.date.available","2018-11-07T11:12:50Z"],["dc.date.issued","2008"],["dc.format.extent","52"],["dc.identifier.isi","000259367100164"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53751"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.issn","0043-5325"],["dc.title","Peripheral T cells are the therapeutic targets of high-dose glucocorticoids in experimental autoimmune encephalomyelitis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]