The Importance of Optical Coherence Tomography in the Diagnosis of Atypical or Subclinical Optic Neuritis: A Case Series Study.

Background: Optic neuritis (ON) is an inflammatory condition of the optic nerve. ON is associated with development of demyelinating diseases of the central nervous system (CNS). CNS lesions visualized by magnetic resonance imaging (MRI) and the finding of oligoclonal IgG bands (OB) in the cerebrospinal fluid (CSF) are used to stratify the risk of MS after a "first" episode of ON. However, the diagnosis of ON in absence of typical clinical manifestations can be challenging. Methods and Materials: Here we present three cases with changes in the optic nerve and ganglion cell layer in the retina over the disease course. (1) A 34-year-old female with a history of migraine and hypertension had suspect amaurosis fugax (transient vision loss) in the right eye. This patient developed MS four years later. Optical coherence tomography (OCT) showed dynamic changes of the thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) over time. (2) A 29-year-old male with spastic hemiparesis and lesions in the spinal cord and brainstem. Six years later he showed bilateral subclinical ON identified using OCT, visual evoked potentials (VEP) and MRI. The patient fulfilled diagnosis criteria of seronegative neuromyelitis optica (NMO). (3) A 23-year-old female with overweight and headache had bilateral optic disc swelling. With OCT and lumbar puncture, idiopathic intracranial hypertension (IIH) was excluded. Further investigation showed positive antibody for myelin oligodendrocyte glycoprotein (MOG). Conclusions: These three cases illustrate the importance of using OCT to facilitate quick, objective and accurate diagnosis of atypical or subclinical ON, and thus proper therapy.

Homonymous visual field defect and retinal thinning after occipital stroke.

INTRODUCTION: Stroke is the most common cause of homonymous visual field defects (VFD). About half of the stroke patients recover from VFD. However, relationship between VFD and retinal changes remains elusive. PURPOSE: To investigate the association between occurrence of VFD, changes of macular ganglion cell and inner plexiform layer (GCIPL) and its axon retinal nerve fiber layer (RNFL) detected with optical coherence tomography (OCT). PATIENTS AND METHODS: The study consists of retrospective review of medical records and follow-up examinations. Patients with acute occipital stroke were registered. VFD was identified with confrontation and/or perimetry tests at the onset. At follow-up, the patients were examined with visual field tests and OCT measurements. RESULTS: Thirty-six patients met the inclusion criteria. At onset, 26 patients (72%) had VFD. At follow-up >1 year after stroke, 13 patients (36%) had remaining VFD: 5 had homonymous hemianopia, 5 had homonymous quadrantanopia, and 3 had homonymous scotomas. Average thickness of GCIPL and RNFL were significantly reduced in each eye in patients with VFD compared to non-VFD (NVFD) (p < .01 for all comparisons). Thickness of superior and inferior RNFL quadrants was significantly reduced in VFD compared to NVFD (p < .01 for both). Among these 13 patients, 4 had characteristic homonymous quadrant-GCIPL thinning, 2 had characteristic homonymous hemi-GCIPL thinning, and 7 had diffuse GCIPL thinning. CONCLUSION: GCIPL and RNFL thinning were observed in the patients with VFD. GCIPL thinning appears in two forms: atypical diffuse thinning, or homonymous hemi-GCIPL thinning. Examining GCIPL and RNFL provides easy and reliable objective measures and is therefore proposed to be of predictive value on visual function.

Retinal changes associated with multivitamin deficiency before and after supplementation.

BACKGROUND: Nutritional visual defects are apparently uncommon nowadays in developed nations. Retinal change-related visual defects caused by hypovitaminoses may be underdiagnosed. AIM OF THE STUDY: To investigate the retinal structural and functional changes in a patient with multivitamin deficiency before and during vitamin supplementation. METHODS: A 51-year-old female had been on vegetarian diet as a child, and on restrict vegan diet during the last 2 years, developing severe bilateral deterioration of visual function and polyneuropathy. Blood test revealed low levels of vitamin A, B6 and D. The patient underwent examinations with optical coherence tomography (OCT), computerized visual field examination (VF), electroretinography (ERG), visual evoked potentials (VEP) and neurography before and after vitamin supplementation. RESULTS: Visual acuity (VA) was 20/1000 and VF examination showed central scotoma in both eyes. Color vision was significantly affected. Full-field ERG showed normal rod and cone function, but a clearly reduced central peak was registered in multifocal ERG (mf-ERG), indicating impaired fovea function. VEP showed delayed latency and low amplitude of P100 in both eyes. Neurography showed sensory polyneuropathy. OCT showed significant thinning of macular ganglion cell plus inner plexiform layer (GCIPL) with rapid progression. Retinal nerve fiber layer (RNFL) was preserved and normal, which is in contrast to neuroinflammatory conditions. After 2.5 years of multivitamin supplementation, the visual functions were improved. GCIPL thickness was stable without further deterioration. CONCLUSIONS: Multivitamin deficiency results in progressive thinning of GCIPL with severe visual deterioration. In contrast to neuroinflammation, RNFL is preserved and normal. Stabilized GCIPL during vitamin supplementation was associated with improved visual function. OCT provides a sensitive and objective measure for differential diagnosis, monitoring retinal change and response to therapy.

Retinal thinning and brain atrophy in early MS and CIS.

BACKGROUND: Optical coherence tomography (OCT) could be complementary to magnetic resonance imaging (MRI) of the brain in monitoring course of multiple sclerosis (MS) and clinically isolated syndrome (CIS). Thinning of neurons in ganglion cell-inner plexiform layer (GCIPL) measured by OCT is assumed to be associated with brain atrophy. OBJECTIVES: To evaluate association of GCIPL with brain parameters detected by quantitative MRI (qMRI) and MR-spectroscopy (MRS) in early MS and CIS. METHODS: Seventeen newly diagnosed MS and 18 CIS patients were prospectively included. The patients were assessed at baseline as well as at 1 year follow-up by OCT, qMRI and MRS. Brain parenchymal and myelin volumes (BPV, MYV respectively) and the corresponding fractions (BPF, MYF) were measured with qMRI. Metabolites including myo-inositol (myo-Ins) were measured in the normal-appearing white matter (NAWM) using MRS. T-tests and ANOVA were used to analyze group differences, and linear regression models to evaluate association of GCIPL with BPV, MYV and myo-Ins after correlation analysis. RESULTS: Disease activity reflected by lesions on MRI and presence of CSF oligoclonal IgG bands were more prominent in MS compared to CIS. GCIPL, BPV, MYV, BPF and MYF were reduced, while concentration of myo-Ins was increased in MS compared to CIS. Follow-up showed consistency of thinner GCIPL in MS compared to CIS. GCIPL thinning correlated with reduced BPV and MYV (P < .05 for both), but with increased myo-Ins (P < .01). CONCLUSIONS: Significant GCIPL thinning occurs in early MS and is associated with enhanced brain inflammation and atrophy.

Benign Multiple Sclerosis is Associated with Reduced Thinning of the Retinal Nerve Fiber and Ganglion Cell Layers in Non-Optic-Neuritis Eyes.

BACKGROUND AND PURPOSE: It is exceedingly difficult to differentiate benign multiple sclerosis (BMS) from relapsing-remitting multiple sclerosis (RRMS) based on clinical characteristics, neuroimaging, and cerebrospinal fluid tests. Optical coherence tomography (OCT) allows quantification of retinal structures, such as the retinal nerve fiber layer (RNFL) thickness, at the optic disc and the ganglion cell layer (GCL) at the macula, on a micrometer scale. It can also be used to trace minor alterations and the progression of neurodegeneration, help predict BMS, and influence the choice of therapy. To utilize OCT to detect the extent of changes of the optic disk and macular microstructure in patients with BMS and RRMS compared to healthy controls (HCs), with special focus on changes related to the presence/absence of optic neuritis (ON). METHODS: Spectral-domain OCT was applied to examine eyes from 36 patients with multiple sclerosis (MS), comprising 11 with BMS and 25 with RRMS, and 34 HCs. RESULTS: The RNFL and GCL were significantly thinner in eyes previously affected by ON, irrespective of the type of MS (i.e., BMS or RRMS), than in HCs. Significant thinning of the GCL was also observed in non-ON RRMS (and not non-ON BMS) compared to HCs. Correspondingly, a significant association between disease duration and thinning rates of the RNFL and GCL was observed only in non-ON RRMS (-0.54±0.24 and -0.43±0.21 µm/year, mean±SE; p<0.05 for both), and not in non-ON BMS (-0.11±0.27 and -0.24±0.24 µm/year). CONCLUSIONS: The RNFL and GCL were thinner in both ON- and non-ON MS, but the change was more pronounced in ON MS, irrespective of the MS subtype studied herein. GCL thinning and the thinning rate of both the GCL and RNFL were less pronounced in non-ON BMS than in non-ON RRMS. These findings may help to predict the course of BMS.

Playing God and the intrinsic value of life: moral problems for synthetic biology?

Most of the reports on synthetic biology include not only familiar topics like biosafety and biosecurity but also a chapter on 'ethical concerns'; a variety of diffuse topics that are interrelated in some way or another. This article deals with these 'ethical concerns'. In particular it addresses issues such as the intrinsic value of life and how to deal with 'artificial life', and the fear that synthetic biologists are tampering with nature or playing God. Its aim is to analyse what exactly is the nature of the concerns and what rationale may lie behind them. The analysis concludes that the above-mentioned worries do not give genuine cause for serious concern. In the best possible way they are interpreted as slippery slope arguments, yet arguments of this type need to be handled with care. It is argued that although we are urged to be especially vigilant we do not have sufficiently cogent reasons to assume that synthetic biology will cause such fundamental hazards as to warrant restricting or refraining from research in this field.

IL-12/IFN-gamma/NO axis plays critical role in development of Th1-mediated experimental autoimmune encephalomyelitis.

The importance of the IL-12/IFN-gamma/nitric oxide (NO) axis in the pathogenesis of autoimmune diseases remains controversial. In parallel experiments, we explored the role of the IL-12/IFN-gamma/NO axis in the development of MOG 35-55-induced experimental autoimmune encephalomyelitis (EAE) in mice lacking IL-12, IFN-gamma receptor (IFN-gammaR) and inducible nitric oxide synthase (NOS2), respectively. In comparison with wide-type control mice, IL-12-/-, IFN-gammaR-/- and NOS2-/- mice displayed more severe clinical signs of EAE both in remission and at subsequent relapse. Given the relatively low IFN-gamma production in IL-12-/- mice and the lack of IFN-gamma/IFN-gammaR signaling pathway in IFN-gammaR-/- mice, IL-12-/-, IFN-gammaR-/- and NOS2-/- mice with EAE exhibited low NO production. This correlated negatively with MOG 35-55-induced T cell proliferation. Both ED1-positive macrophages and CD4-positive T cells were increased in spinal cords from IL-12-/-, IFN-gammaR-/- and NOS2-/- compared to control mice. In vitro experiments demonstrate that spleen mononuclear cells from IL-12-/-, IFN-gammaR-/- and NOS2-/-mice with EAE present stronger migration capacity when compared to control mice. These results reveal that the IL-12/IFN-gamma/NO axis plays a critical role in the development of MOG 35-55-induced EAE, possibly over failing NO production.

Cell biology and clinical promise of G-CSF: immunomodulation and neuroprotection.

In the light of the enthusiasm to use of recombinant human granulocyte colony-stimulating factor (G-CSF) for immunomodulation and neuroprotection, it should be remembered that the current knowledge is based on a century of laborious research. G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis. Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration. Here, we describe the immunomodulation and the neuroprotection that can be achieved with G-CSF, and summarize possible mechanisms of G-CSF as a potential therapeutic agent in autoimmune diseases and neurological disorders. Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

Multiple Sclerosis and HERV-W/MSRV: A Multicentric Study.

We designed a large multicentric study to analyse the presence of MSRV particles in blood and CSF of a large cohort of patients and controls from different European areas. 149 MS patients and 153 neurological and healthy controls were selected from Sardinia, Spain, Northern-Italy and Sweden. To avoid biological and inter-assay variability MSRV was detected within a single laboratory through nested and real-time PCR assays specific for pol and env genes. MSRV detection in blood and CSF of MS patients and controls in populations of different ethnicity gave significant differences (p<0.05 compared to neurological controls and <0.001 compared to healthy controls). The presence and viral load of MSRV are significantly associated with MS as compared to neurological and healthy controls in all ethnic groups.

Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness.

Two or more oligoclonal IgG bands (OB) detected by separation of cerebrospinal fluid (CSF) proteins while not demonstrable in corresponding serum reflect a local B-cell response accompanying central nervous system (CNS) inflammation. Using optimized, standardized methodology, preferentially protein separation by isoelectric focusing followed by immunoblotting, more than 95% of patients with multiple sclerosis (MS) have CSF OB of IgG class not detectable in serum, thereby providing powerful evidence for the diagnosis of MS. Once present, CSF OB persists in the individual patient irrespective of MS course or therapy. Because of the high sensitivity of CSF OB in MS as well as its high specificity in the appropriate clinical setting, examination of CSF for OB of IgG class can be strongly recommended to obtain support for the diagnosis of MS and identify patients with clinically isolated syndrome (CIS) at increased risk of developing MS. The IgG index equal to CSF/serum IgG:CSF/serum albumin is elevated in about 70% of MS patients, but rarely in CSF OB-negative MS. Because of lower diagnostic sensitivity, IgG index cannot be recommended as replacement of CSF OB in the diagnosis of MS but, when elevated, as additional evidence for an augmented B-cell response within the CNS that is compatible with MS. Although the clinical picture as well as findings from magnetic resonance imaging of the brain and spinal cord are essential for an MS diagnosis, this should be re-evaluated in CSF OB-negative patients, keeping in mind the many disease entities imitating MS. Recommended diagnostic criteria for MS must include definitions of the role of lumbar puncture and of clearly specified, optimized and standardized routine CSF investigations including for the presence of CSF IgG OB. There is a need for concerted long-term follow-up studies of the subgroup of MS patients without CSF OB regarding e.g. prognostic and immunologic features. For inclusion in trials of disease-modulating drugs, it is recommended that patients with MS or CIS are selected regarding presence vs. absence of CSF OB. Development and evaluation of new technologies to define local vs. systemic B-cell responses in patients with MS or CIS vs. patients with other inflammatory neurological diseases should shed new light on the role of CSF OB, which remains enigmatic.

Tolerogenic dendritic cells: the ins and outs of outcome.

Recent studies point to an important role for dendritic cells (DCs) in the induction of peripheral tolerance, revealing that the maturation and/or activation state of DCs might be a control point for the induction of peripheral tolerance. Recent progress in our understanding of the mechanisms mediating immune tolerance indicates them to be far more complex than hitherto anticipated. Factors deciding the outcome of vaccination with autologous DCs to prevent and treat diseases with an autoimmune background include maturation state of DCs, their administration route, long-term effects, antigen loading, and in vivo microenvironment. DC vaccination, although promising, is far from standardized. In this review, we discuss the ins and outs of DC-mediated immune tolerance and the need for careful experimental design to unequivocally prove the efficacy and reach the goal of optimized use of DCs in autoimmune diseases.

CD24 and myosin light polypeptide 2 are involved in prevention of experimental autoimmune encephalomyelitis by myelin basic protein-pulsed dendritic cells.

We previously demonstrated that injection of myelin basic protein-pulsed (MBP-pulsed)--but not of unpulsed--autologous bone marrow-derived dendritic cells (DC) efficiently prevents experimental autoimmune encephalomyelitis (EAE) in Lewis rats. To define the molecules involved, we used 3 groups of rats pretreated subcutaneously with MBP-DC, or unpulsed DC, or PBS (control EAE). Four weeks later, all rats were immunized with encephalitogenic MBP peptide and adjuvant. Microarray analyses were done to screen for genes that differ among the 3 groups. Based on microarray analysis data, we used real-time PCR to measure expression of six probably involved genes in draining lymph node cells obtained on day 0, day 7 and day 14 post immunization (p.i.). Two of these 6 genes were consistently altered in both microarray analyses and RT-PCR. They are CD24 antigen being persistently low, and myosin light polypeptide 2 (Myl2) being high in the acute immune response in MBP-DC pretreated rats that develop resistance to EAE. These two genes could be targeted to treat EAE and, possibly, multiple sclerosis.

Autoantigen-pulsed dendritic cells constitute a beneficial cytokine and growth factor network in ameliorating experimental allergic encephalomyelitis.

Injection of myelin basic protein (MBP)-pulsed dendritic cells (DC) into healthy rats, as we reported before and observed in this study, did not induce clinical experimental allergic encephalomyelitis (EAE), but effectively protected the rats from subsequent EAE induction. The mechanisms by which MBP-pulsed DC mediate immune protection are not completely understood. In the present study, we mainly explored the dynamic change of cytokine and growth factor mRNA expression in spinal cords after subcutaneous injection of MBP-pulsed and unpulsed DC. The expression of interleukin (IL)-1, interferon-gamma and tumour necrosis factor-alpha as well as programmed death ligand (PDL)-1, PDL-2, signal transducer and activator of transcription (STAT)4, STAT6, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-2 was increased on day 0 postimmunization (p.i.). The increase of IL-12 expression was observed on day 7 p.i., while the increase of IL-10 expression mainly occurred on day 14 p.i. Except downregulation of insulin-like growth factor-1, the expression of brain-derived neurotrophic factor, ciliary neurotrophic factor, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-B/C as well as nerve growth factor receptor (NGF-R), FGF receptor, PDGF-R-alpha and beta was elevated on day 0 p.i., while the increase of TIMP and NGF was observed on days 0 and 7 p.i. There were no significant differences on MMP-2, spinal cord-derived growth factor and PDGF-A mRNA expression. In line with the suppression of EAE induced by MBP-pulsed DC, the dynamic change of cytokines and growth factors in spinal cords should constitute a beneficial microenvironment against EAE.

Anti-inflammatory nuclear receptor superfamily in multiple sclerosis patients from Sardinia and Sweden.

Several nuclear hormone receptors have been associated with inflammatory reactions. Particularly, liver X receptors (LXRs) have recently been identified as key transcriptional regulators of genes involved in lipid homeostasis and inflammation. LXRs are negative regulators of macrophage inflammatory gene expression. Multiple sclerosis (MS), a demyelinating disease of the central nervous system of unknown cause, is characterized by recurrent inflammation involving macrophages and their inflammatory mediators. Sweden belongs to the countries with a high MS incidence. In Italy, the MS incidence is lower, except on the island of Sardinia where the incidence is even higher than in Sweden. Subjects from Sardinia are ethnically more homogeneous, and differ from Swedes also regarding genetic background and environment. We studied mRNA expression of several nuclear hormone receptors in blood mononuclear cells (MNC) from female patients with untreated relapsing-remitting MS from Sassari, Sardinia, and Stockholm, Sweden. Sex- and age-matched healthy controls (HC) were from both areas. mRNA expression was evaluated by quantitative real-time PCR. We found altered mRNA expression of LXRs, estrogen receptors (ERs), and androgen receptor (AR) in MS. mRNA expression of both LXRalpha and LXRbeta is lower in MS from Stockholm but not from Sassari. In particular, LXRalpha mRNA expression was significantly lower in MS from Stockholm as compared with all groups in the study including MS from Sassari. Low levels of ERalpha mRNA are seen in MS from both Stockholm and Sassari. The splice variant ERbetacx showed significantly higher mRNA expression in MS from Sassari and Stockholm as compared with corresponding HC. In particular, ERbetacx mRNA in MS from Sassari was remarkably higher as compared with all other groups in the study. Higher levels of AR mRNA are present in HC from Sassari. The findings indicate that the expression levels of anti-inflammatory nuclear receptor superfamily genes in MS appear to reflect both ethnic and environmental influences.

Immunological heterogeneity of multiple sclerosis in Sardinia and Sweden.

Subjects from Sardinia, Italy, are relatively homogeneous compared to Swedes. Although ethnically distant, both populations have similarly high multiple sclerosis (MS) incidence rates. Pro- and anti-inflammatory cytokines and their receptors, signalling molecules and other immune response-associated factors might influence MS pathogenesis, though definite proof is missing. The study of populations with similar MS incidence but different genetic and environmental background could make possible the definition of factors that relate to such background differences. We selected untreated female MS patients from Sassari, Sardinia, and Stockholm, Sweden, and corresponding sex- and age-matched healthy controls (HC), to study blood mononuclear cells (MNC) for mRNA expression of 20 immune response-related genes considered relevant in MS, employing real-time PCR. Higher expression of IL-12p40 mRNA was confined to MS from both Sassari and Stockholm, compared to corresponding HC. MS patients from Sassari, but not Stockholm, expressed higher TNF-alpha compared to corresponding HC. MS patients from Stockholm, but not Sassari, expressed higher IL-6. Indoleamine 2,3 dioxygenase (IDO), a molecule necessary in tolerance induction, was lower in MS from Stockholm compared to corresponding HC. This was not observed in Sassari. No differences were detected for other members of the IL-12 family, other Th1 and Th2 cytokines, and the signalling molecules Stat 4 and 6. The results corroborate a pro-inflammatory state in MS as reflected by high expression of IL-12, TNF-alpha and IL-6, although the extent of expression of TNF-alpha, IL-6 and IDO differs between strictly matched MS patients from different high-incidence areas. This might result from genetic and/or environmental differences. They may account for some of the discrepancies regarding immune response-related molecules previously reported in MS. In conclusion, a pro-inflammatory state exists in MS patients from Sassari as well as Stockholm. The changes of pro-inflammatory and other immune response-related variables differ however between the two MS populations. This may be attributed to the genetic and/or environmental background.

Long-term effects of IFN-gamma, IL-10, and TGF-beta-modulated dendritic cells on immune response in Lewis rats.

Increasing data have shown that IFN-gamma, IL-10, and TGF-beta-modulated dendritic cells (DC) provide a promising strategy in treatment of experimental allergic encephalomyelitis and experimental autoimmune myasthenia gravis through different manner. To explore the immune response status after long-term application of these cytokine-modulated-DC, Lewis rats were injected subcutaneously into naive DC and IFN-gamma, IL-10, and TGF-beta-modulated DC (i.e., IFN-gamma-DC, IL-10-DC, and TGF-beta-DC) at does of 1 x 10(6) cells/rat every month for continuous 18 months, respectively. No rats suffered from decreased vigor and activity as well as cachectic condition during 18-month observation, and no rats had body-weight loss after 18-month treatment. Exploratory laparectomy did not find any tumor in all rats. IL-10-DC and TGF-beta-DC resulted in lower nonspecific (Con A-induced) and antigen specific (ovalbumin-stimulated) spleen mononuclear cells proliferation, accompanied by lower levels of IFN-gamma, IL-10, and TNF-alpha. On the contrary, IFN-gamma-DC did not suppress cell proliferation and IFN-gamma and IL-10 production except only slightly decreased TNF-alpha levels. These results suggest that IFN-gamma-DC seems to be a more ideal candidate in the treatment of autoimmune diseases without suppressing immune response.

Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell-indoleamine 2,3-dioxygenase axis.

Estrogen results in the suppression of experimental allergic encephalomyelitis (EAE), a frequently used experimental animal model of multiple sclerosis (MS). The mechanism by which estrogen acts in diseases with an autoimmune background is less clear. Here, we used splenic dendritic cells (DC) from the Lewis rats EAE model as target cells, and explored the pathway of estrogen in immune modulation. Estrogen did not affect the expression of MHC class II, CD80 and CD86 by DC, but inhibited the ability of DC to stimulate T cell proliferation and production of both Th1 and Th2 cytokines. This was accompanied by increased T cell apoptosis. Estrogen up-regulated DC to express indoleamine 2,3-dioxygenase (IDO) which can limit T cell responses. The effects of estrogen-exposed DC on T cell proliferation and apoptosis were partly abolished by addition of an IDO inhibitor (1-methyl-dl-tryptophan, 1-MT), indicating that estrogen-exposed DC induced IDO-dependent T cell suppression. Our data support the hypothesis that the estrogen-induced suppression of EAE, as well as the reduction in number of MS relapses observed during pregnancy, may be related to the estrogen-DC-IDO axis. This observation could open up a novel therapeutic target for influencing the course of MS and other diseases with an autoimmune diseases background.

Laquinimod (ABR-215062) suppresses the development of experimental autoimmune encephalomyelitis, modulates the Th1/Th2 balance and induces the Th3 cytokine TGF-beta in Lewis rats.

The new orally active drug laquinimod (ABR-215062) was evaluated in experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. EAE shares important immunological and clinical features with multiple sclerosis (MS). Doses of 16, 1.6 and 0.16 mg/kg/day laquinimod dose-dependently inhibited disease and showed better disease inhibitory effects as compared to roquinimex (Linomide). Furthermore, laquinimod inhibited the inflammation of both CD4+ T cells and macrophages into central nervous tissues, i.e. the spinal cord. It also changed the cytokine balance in favour of TH2/TH3 cytokines IL-4, IL-10 and TGF-beta. Laquinimod therefore represents a new orally active immunoregulatory drug without general immunosuppressive properties with a potential for the treatment of severe autoimmune diseases like MS.