Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis.


:We examined immune function and changes in T cell populations over a 1-year period in a series of progressive multiple sclerosis (MS) patients treated with different regimens of cyclophosphamide/ACTH as part of the Northeast Multiple Sclerosis Treatment Group. Our studies were designed to determine the effect of different cyclophosphamide/ACTH regimens on T cell populations and functional immune assays and to determine whether immune measures could be identified to predict which patients responded favorably to treatment. Cyclophosphamide/ACTH infusions significantly decreased the proportion of peripheral blood CD4+ T cells at 2, 6 and 12 months following treatment while there was a tendency for increased CD8 expression. This was associated with significant decreases of CD4/CD8 ratios at 2, 6 and 12 months following treatment compared to pretreatment. No changes in CD3+ T cells were observed while there were increased percentages of CDw26 (Ta1) positive and IL-2 positive T cells following treatment. The only T cell populations predictive of improvement were percentages of either CD3+ or CD4+ cells where increased percentages of either these populations at 2 months following cyclophosphamide/ACTH infusions were associated with improvement at both 6 and 12 months. In terms of functional immune measures, we found that cyclophosphamide/ACTH treatment decreased the level of proliferation in the allogeneic mixed lymphocyte reaction (MLR) at 2 months and of spontaneous proliferation of mononuclear cells at 12 months following therapy. Changes in spontaneous proliferation were predictive of clinical improvement at 12 months in that subjects with improved scores on the disability status scale (DSS) had decreases in spontaneous proliferation at 12 months as compared to pretreatment, whereas those stable or worse did not change significantly. Thus, our studies have demonstrated specific alterations in immune function following immunosuppression with cyclophosphamide/ACTH and suggest that certain immune measures may be linked to a positive clinical response and thus associated with disease progression in MS.


J Neuroimmunol


Hafler DA,Orav J,Gertz R,Stazzone L,Weiner HL




Has Abstract


1991-05-01 00:00:00














  • A novel protective model against experimental allergic encephalomyelitis in mice expressing a transgenic TCR-specific for myelin oligodendrocyte glycoprotein.

    abstract::Myelin oligodendrocyte glycoprotein (MOG) is an important autoantigen in multiple sclerosis and in experimental autoimmune encephalomyelitis (EAE). We generated a T cell receptor (TCR) transgenic (Tg) mouse expressing a TCR derived from an encephalitogenic T cell clone specific for MOG(35-55). This mouse failed to dev...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Mendel I,Natarajan K,Ben-Nun A,Shevach EM

    更新日期:2004-04-01 00:00:00

  • The localisation of fibrin, fibronectin and class II major histocompatibility complex antigen in the spinal cord in chronic relapsing experimental allergic encephalomyelitis.

    abstract::Light and electron immunocytochemistry using antibodies recognising a class II major histocompatibility complex antigen, fibrin, fibronectin, albumin and factor VIII related antigen has been used to stain sections of spinal cord from normal guinea pigs and those with chronic relapsing experimental allergic encephalomy...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Butter C,Healey DG,Agha N,Wilcox CE,Antoniou AV,Turk JL

    更新日期:1989-03-01 00:00:00

  • The expression of complement regulatory proteins by adult human oligodendrocytes.

    abstract::In multiple sclerosis, infiltrating T lymphocytes and perivascular microglia may initiate demyelinating lesions, but a role for antibody and complement in the ensuing inflammatory damage to myelin and oligodendrocytes is likely. In most tissues, ubiquitously expressed complement regulatory proteins prevent autologous ...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Scolding NJ,Morgan BP,Compston DA

    更新日期:1998-04-01 00:00:00

  • Band 1 and voltage-sensitive Na+ channels are not codistributed in cultured rodent neuronal cells.

    abstract::The relationship of the mouse nervous system specific band 1 protein to the putative high molecular weight component of the Na+ channel was investigated using antibody to band 1. Morphologic differentiation of cultured neuroblastoma cells has been reported to increase the quantity of the putative Na+ channel high mole...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Akeson R,Graham K

    更新日期:1981-09-01 00:00:00

  • Microarray analysis of IFN-gamma response genes in astrocytes.

    abstract::IFN-gamma (IFN-gamma) has been shown to activate astrocytes to acquire immune functions. In this study the effect of IFN-gamma on murine astrocytes was investigated via microarray analysis. The activating effect of IFN-gamma on the astrocyte transcriptome showed predominance toward pathways involved in adaptive immuni...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Halonen SK,Woods T,McInnerney K,Weiss LM

    更新日期:2006-06-01 00:00:00

  • PD-1 immune checkpoint blockade promotes brain leukocyte infiltration and diminishes cyst burden in a mouse model of Toxoplasma infection.

    abstract::Tissue cysts, the hallmark of chronic Toxoplasma gondii infection, are predominantly located in the brain making clearance of the parasite difficult. Currently available anti-T. gondii drugs are ineffective on cysts and fail to prevent reactivation of latent toxoplasmosis. We examined whether abrogation of inhibitory ...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Xiao J,Li Y,Yolken RH,Viscidi RP

    更新日期:2018-06-15 00:00:00

  • MS susceptibility is not affected by single nucleotide polymorphisms in the MMP9 gene.

    abstract::Matrix metalloproteinase 9 (MMP9) plays an important role in the pathogenesis of multiple sclerosis (MS). However, the impact of genetic variants affecting MMP9 on MS susceptibility is still in debate. We could not detect an association of MMP9 SNPs with MS on a genome-wide significance level by SNP genotyping, follow...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Nischwitz S,Wolf C,Andlauer TF,Czamara D,Zettl UK,Rieckmann P,Buck D,Ising M,Bettecken T,Mueller-Myhsok B,Weber F

    更新日期:2015-02-15 00:00:00

  • Differential effects on glial activation by a direct versus an indirect thrombin inhibitor.

    abstract::Thrombin is a potent regulator of brain function in health and disease, modulating glial activation and brain inflammation. Thrombin inhibitors, several of which are in clinical use as anti-coagulants, can reduce thrombin-dependent neuroinflammation in pathological conditions. However, their effects in a healthy CNS a...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Marangoni MN,Braun D,Situ A,Moyano AL,Kalinin S,Polak P,Givogri MI,Feinstein DL

    更新日期:2016-08-15 00:00:00

  • A novel calpain inhibitor for the treatment of acute experimental autoimmune encephalomyelitis.

    abstract::Aberrant activation of calpain plays a key role in the pathophysiology of several neurodegenerative disorders. Calpain is increasingly expressed in inflammatory cells in EAE and is significantly elevated in the white matter of patients with multiple sclerosis, thus calpain inhibition could be a target for therapeutic ...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Hassen GW,Feliberti J,Kesner L,Stracher A,Mokhtarian F

    更新日期:2006-11-01 00:00:00

  • Characterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: Effects of oligomeric and fibrillar amyloid-beta.

    abstract::M1 and M2 are the extremes of the differentiation spectrum of activated macrophages. Since microglia are members of the same cell lineage, we have characterized their transcription profile and their phagocytic activity under different conditions. LPS or IFN-gamma induce a M1-like phenotype, while IL-10 or IL-4 differe...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Michelucci A,Heurtaux T,Grandbarbe L,Morga E,Heuschling P

    更新日期:2009-05-29 00:00:00

  • Narcolepsy and the HLA region.

    abstract::Narcolepsy was first shown to be tightly associated with HLA-DR2 and DQ1 in 1983, suggesting a possible autoimmune mechanism. Early investigations failed to demonstrate this hypothesis, postulating that HLA-DR2 was only a linkage marker for another, unknown narcolepsy-causing gene. The autoimmune hypothesis is now bei...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章,评审


    authors: Lin L,Hungs M,Mignot E

    更新日期:2001-07-02 00:00:00

  • T cell response to myelin basic protein in the context of the multiple sclerosis-associated HLA-DR15 haplotype: peptide binding, immunodominance and effector functions of T cells.

    abstract::In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myeli...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Vergelli M,Kalbus M,Rojo SC,Hemmer B,Kalbacher H,Tranquill L,Beck H,McFarland HF,De Mars R,Long EO,Martin R

    更新日期:1997-08-01 00:00:00

  • Increase of Ki-67+ natural killer cells in multiple sclerosis patients treated with interferon-β and interferon-β combined with low-dose oral steroids.

    abstract::Interferon-β (IFN-β) is known to expand regulatory CD56(bright) natural killer (NK) cells in multiple sclerosis (MS). In this cross-sectional study we show that MS patients treated with IFN-β alone or in combination with low-dose prednisolone displayed increased proportion of all NK cell subsets in the active phase of...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Sanvito L,Tomita A,Chihara N,Okamoto T,Lin Y,Ogawa M,Gran B,Aranami T,Yamamura T

    更新日期:2011-07-01 00:00:00

  • Cytokine and IL-12 receptor mRNA discriminate between different clinical subtypes in multiple sclerosis.

    abstract::Little is known about the involvement of cytokines in the pathogenesis of primary progressive (PP) multiple sclerosis (MS). We evaluated in this cross-sectional study whether IL-18, IL-12p35, IL-12p40, TNF-alpha, IFN-gamma, IL-10, IL-4, TGF-beta, IL-12Rbeta1, and IL-12Rbeta2 mRNA expression in unstimulated white blood...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: van Boxel-Dezaire AH,Smits M,van Trigt-Hoff SC,Killestein J,van Houwelingen JC,Polman CH,Nagelkerken L

    更新日期:2001-11-01 00:00:00

  • Soluble Fas (Apo-1) levels in cerebrospinal fluid of multiple sclerosis patients.

    abstract::CSF and serum levels of soluble Fas were studied in MS patients, in patients with various neurological diseases and in healthy controls. We did not detect differences in serum sFas levels between MS patients and controls. In CSF, despite sFas levels being similar in all patients studied, a statistically significant co...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Ciusani E,Frigerio S,Gelati M,Corsini E,Dufour A,Nespolo A,La Mantia L,Milanese C,Massa G,Salmaggi A

    更新日期:1998-02-01 00:00:00

  • Characterization of naïve, memory and effector T cells in progressive multiple sclerosis.

    abstract::We characterized naïve, central memory (CM), effector memory (EM) and terminally differentiated effector memory (TEMRA) CD4+ and CD8+ T cells and their expression of CD49d and CD26 in peripheral blood in patients with multiple sclerosis (MS) and healthy controls. CD26+ CD28+ CD4+ TEMRA T cells were increased in all su...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Nielsen BR,Ratzer R,Börnsen L,von Essen MR,Christensen JR,Sellebjerg F

    更新日期:2017-09-15 00:00:00

  • Class II major histocompatibility complex (MHC) gene expression in the mouse brain is elevated in the autoimmune MRL/Mp-lpr/lpr strain.

    abstract::Brain levels of Ia mRNA, quantified by RNA blot analysis, were found to be 30-50-fold lower than splenic levels in all autoimmune and normal mouse strains examined except MRL/l, whose brain content of Ia mRNA was comparable to normal splenic levels. Prior perfusion to remove blood cells did not alter the amount of Ia ...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: McIntyre KR,Ayer-LeLièvre C,Persson H

    更新日期:1990-06-01 00:00:00

  • How cytokines can influence the brain: a role for chemokines?

    abstract::Following inflammation or infection, cytokines are released in the blood. Besides their effect on the immune system, cytokines can also act in the brain to modulate our behaviors, inducing for example anorexia when produced in large amount. This review focuses on our current knowledge on how cytokines can influence th...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章,评审


    authors: Guyon A,Massa F,Rovère C,Nahon JL

    更新日期:2008-07-31 00:00:00

  • Production of interleukin-1 receptor antagonist by human glioblastoma cells in vitro and in vivo.

    abstract::We investigated the expression and production of the interleukin-1 receptor antagonist (IL-1ra) in three human glioblastoma cell lines (LN443, LN444, LN859). Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated the expression of IL-1ra mRNA transcripts in the three cell lines. These three cell lines a...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Tada M,Diserens AC,Desbaillets I,Jaufeerally R,Hamou MF,de Tribolet N

    更新日期:1994-03-01 00:00:00

  • Interferon-gamma-inducible genes in primary glial cells of the central nervous system: comparisons of astrocytes with microglia and Lewis with brown Norway rats.

    abstract::We compared the expression of various interferon-gamma (IFN-gamma)-inducible mRNAs in primary rat astrocytes and microglia. Of 11 different mRNAs inducible by IFN-gamma in a macrophage cell line, RAW 264.7, only eight were induced in both types of glia, which included mRNAs encoding the transcriptional factors, IRF-1,...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Vanguri P

    更新日期:1995-01-01 00:00:00

  • Involvement of JAK/STAT signaling in the effect of cornel iridoid glycoside on experimental autoimmune encephalomyelitis amelioration in rats.

    abstract::In the present study, we investigated the therapeutic benefit of cornel iridoid glycoside (CIG), the main component extracted from Cornus officinalis, in experimental autoimmune encephalomyelitis (EAE) rats. CIG was intragastrically administered daily after EAE initiation for 20days and reduced disease severity, incid...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Yin L,Chen Y,Qu Z,Zhang L,Wang Q,Zhang Q,Li L

    更新日期:2014-09-15 00:00:00

  • The role of exosomes in CNS inflammation and their involvement in multiple sclerosis.

    abstract::Multiple sclerosis (MS) is a putative autoimmune disease of the central nervous system (CNS) in which autoreactive immune cells recognizing myelin antigens lead to demyelination and axonal injury. Mechanisms relevant to the pathogenesis of MS have not been fully elucidated, particularly those underlying initiation of ...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章,评审


    authors: Selmaj I,Mycko MP,Raine CS,Selmaj KW

    更新日期:2017-05-15 00:00:00

  • ELI-spot of Th-1 cytokine secreting PBMC's in multiple sclerosis: correlation with MRI lesions.

    abstract::The Th1-like cytokines, interleukin 2 (IL-2), interferon gamma (IFN-gamma), and lymphotoxin alpha (LT-alpha) have been implicated in the immunopathogenesis of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), an animal model of immune mediated demyelination. These cytokines have been associate...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Calabresi PA,Fields NS,Farnon EC,Frank JA,Bash CN,Kawanashi T,Maloni H,Jacobson S,McFarland HF

    更新日期:1998-05-15 00:00:00

  • Exposure to forced swim stress alters morphofunctional characteristics of the rat thymus.

    abstract::The aim of this study was to investigate whether chronic stress, induced by repeated daily swimming during 21 days, alters the morphofunctional parameters in the thymus of adult rats. Our results showed that chronic stress reduced thymus mass, total number of thymocytes, volume of the thymus compartments and numerical...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Zivković IP,Rakin AK,Petrović-Djergović DM,Kosec DJ,Mićić MV

    更新日期:2005-03-01 00:00:00

  • Encephalitogenic and immunogenic potential of myelin-associated glycoprotein (MAG), oligodendrocyte-specific glycoprotein (OSP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in ABH and SJL mice.

    abstract::Synthetic peptides of myelin-associated glycoprotein (MAG), oligodendrocyte-specific glycoprotein (OSP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) were screened for their ability to induce experimental allergic encephalomyelitis (EAE) in ABH (H-2A(g7)) and SJL (H-2(s)) mice. The use of overlapping 16mer...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Morris-Downes MM,McCormack K,Baker D,Sivaprasad D,Natkunarajah J,Amor S

    更新日期:2002-01-01 00:00:00

  • B1 cells are unaffected by immune modulatory treatment in remitting-relapsing multiple sclerosis patients.

    abstract::In this study we aimed to investigate whether treatment with an immune modulatory drug had an effect on the distribution of B cell subpopulations in patients with remitting-relapsing multiple sclerosis (RRMS). We investigated the first-line drugs glatiramer acetate, interferon-β and natalizumab. Our data show that the...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Rovituso D,Heller S,Schroeter M,Kleinschnitz C,Kuerten S

    更新日期:2014-07-15 00:00:00

  • Elevated cerebrospinal fluid CD4+/CD8+ T cell ratio in myasthenia gravis.

    abstract::The proportions of CD2+, CD4+ and CD8+ lymphocytes were determined with the 3-layer indirect immunoperoxidase technique in the cerebrospinal fluid (CSF) of 31 patients with myasthenia gravis (MG) and 21 control subjects without autoimmune or central nervous system (CNS) diseases. None of the MG patients were using imm...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Müller KM,Taskinen E,Iivanainen M

    更新日期:1990-12-01 00:00:00

  • Chemokine receptor expression on MBP-reactive T cells: CXCR6 is a marker of IFNgamma-producing effector cells.

    abstract::Cytokine-polarized T cells have distinct chemokine receptor (CKR) expression patterns associated with their cytokine secretion profiles. In order to investigate this paradigm in autoreactive human T cells, we have determined the CKR expression pattern of myelin basic protein (MBP)-reactive T cell lines (TCL) and compa...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Calabresi PA,Yun SH,Allie R,Whartenby KA

    更新日期:2002-06-01 00:00:00

  • Monocytes in active multiple sclerosis: intact regulation of HLA-DR density in vitro despite decreased HLA-DR density in vivo.

    abstract::HLA-DR expression on circulating monocytes varies as a function of disease activity in patients with multiple sclerosis (MS), a putative immunopathological demyelinating disorder. Specifically, monocytes isolated from subjects with active MS exhibit reduced HLA-DR antigen density, and immunoregulatory aberrations such...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Ransohoff RM,Tuohy VK,Barna BP,Rudick RA

    更新日期:1992-04-01 00:00:00

  • The HuD paraneoplastic protein shares immunogenic regions between PEM/PSN patients and several strains and species of experimental animals.

    abstract::Patients with small-cell carcinoma of the lung and paraneoplastic encephalomyelitis develop antibodies (anti-Hu) against HuD, a member of a family of neuronal specific RNA-binding proteins, which are also expressed by the tumor. In order to determine if the human HuD paraneoplastic antigen shares immunogenic regions b...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章


    authors: Sillevis Smitt P,Manley G,Dalmau J,Posner J

    更新日期:1996-12-01 00:00:00