Ingested (oral) adrenocorticotropic hormone (ACTH) inhibits interleukin-17 in the central nervous system after adoptive transfer of T helper (Th)1/Th17 T cells in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis.

Background: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system (CNS) that resembles multiple sclerosis (MS) and provides a useful animal model for the evaluation of mechanisms of action for potential immunomodulatory therapies. We have previously shown that oral adrenocorticotropic hormone (ACTH) decreased either interleukin (IL)-17 and/or interferon (IFN)γ in the CNS during EAE.

Objective: We wanted to examine whether oral ACTH showed a preferential effect on Th17 as opposed to Th1 phenotypes.

The genealogy, methodology, similarities and differences of immune reconstitution therapies for multiple sclerosis and neuromyelitis optica.

Immune reconstitution therapies (IRTs) are a type of short course procedure or pharmaceutical agent within the MS pharmacopeia. They emanate from oncology and induce transient incomplete lympho-ablation with or without myelo-ablation, resulting in potential prolonged immunomodulation. Thus, they provide significant prophylaxis from disease activity without retreatment.

Ingested (Oral) Adrenocorticotropic Hormone Inhibits IL-17 in the Central Nervous System in the Mouse Model of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the CNS that resembles multiple sclerosis and provides a useful animal model for the evaluation of mechanisms of action for potential immunomodulatory therapies. We have previously shown that oral adrenocorticotropic hormone (ACTH) decreased IL-17 in the gut lamina propria and the spleen and increased CD4 Foxp3 T regulatory cells and IL-10 in the spleen during EAE in the C57BL/6 mouse. However, we did not investigate the specific cellular alterations of proinflammatory and anti-inflammatory factors in the CNS.

The immunomodulatory effects of social isolation in mice are linked to temperature control.

Living in isolation is considered an emerging societal problem that negatively affects the physical wellbeing of its sufferers in ways that we are just starting to appreciate. This study investigates the immunomodulatory effects of social isolation in mice, utilising a two-week program of sole cage occupancy followed by the testing of immune-inflammatory resilience to bacterial sepsis. Our results revealed that mice housed in social isolation showed an increased ability to clear bacterial infection compared to control socially housed animals.

Anti-Inflammatory Agents: An Approach to Prevent Cognitive Decline in Alzheimer's Disease.

Systemic inflammation is an organism's response to an assault by the non-self. However, that inflammation may predispose humans to illnesses targeted to organs, including Alzheimer's disease (AD). Lesions in AD have pro-inflammatory cytokines and activated microglial/monocyte/macrophage cells.

A proposal: How to study pro-myelinating proteins in MS.

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the CNS. An unmet need in MS is repair i.e.

Immune reconstitution therapy in NMOSD.

Importance: NMO spectrum disorders [NMOSD] is a relapsing autoimmune disorder with attacks of optic neuritis (ON) and transverse myelitis (TM). A large proportion of NMOSD patients have no or a partial recovery after relapse.

Observations: The neuro-immunological community now has a number of indicated agents for NMOSD therapy including eculizumab [Soliris®], inebilizumab (Uplizna®) and satralizumab (Enspryng®) with different mechanisms of action (MOA), rapidity of the onset of action (OOA) and issues of long-term safety.

Plegia to walking: AHSCBMT in severe NMOSD relapse.

Objectives: Neuromyelitis optica is a devastating, relapsing, inflammatory, autoimmune disorder characterised in large part by attacks of optic neuritis and transverse myelitis causing blindness and plegia in many patients. Eighty-three per cent of patients with transverse myelitic attacks and 67% of patients with optic neuritis attacks have no or a partial recovery.

Methods: Results from The European Group for Blood and Marrow Transplantation Autoimmune Diseases Working Party imply failure of autologous haematopoietic stem cell bone marrow transplantation.

Review of approved NMO therapies based on mechanism of action, efficacy and long-term effects.

Importance: Neuromyelitis optica (NMO - including NMO spectrum disorders [NMOSD]) is a devastating disease. Eighty-three percent of patients with transverse myelitic (TM) attacks and 67% of patients with optic neuritis (ON) attacks have no or a partial recovery.

Observations: Up until recently, there was no proven agent to treat to prevent relapses.

In MS: Immunosuppression is passé.

Importance: Prolonged and significant alterations of the immune system by immunosuppression makes multiple sclerosis (MS) patients susceptible to opportunistic infections and malignancies over long periods of treatment.

Observations: A reasonable clinical and practical definition of immunosuppression is a temporary or permanent alteration of the body's immune system and subsequent lack of ability to fight infections and malignancies. Immunosurveillance is the sine qua non of the immune system.

Ingested ACTH blocks Th17 production by inhibiting GALT IL-6.

Background: EAE is an inflammatory autoimmune process of the CNS that resembles multiple sclerosis (MS) and provides a useful animal model for the evaluation of mechanisms of action for potential immunomodulatory therapies. Oral ACTH (adrenocorticotropic hormone) can decrease clinical disease, IL-17 and Th1-like encephalitogenic IFN-γ secretion and increase T frequency. The mechanism by which oral ACTH decreases inflammatory proteins and increases T cell frequencies is unknown.

Clinical and MRI efficacy of sc IFN β-1a tiw in patients with relapsing MS appearing to transition to secondary progressive MS: post hoc analyses of PRISMS and SPECTRIMS.

This study evaluated efficacy of subcutaneous (sc) interferon beta-1a (IFN β-1a) 44 µg 3 × weekly (tiw) in patients appearing to transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS). The PRISMS study included 560 patients with RRMS (EDSS 0-5.0; ≥ 2 relapses in previous 2 years), and the SPECTRIMS study included 618 patients with SPMS (EDSS 3.

Tumefactive demyelination: Clinical outcomes, lesion evolution and treatments.

Objective: Large demyelinating lesions with possible mass effect (tumefactive multiple sclerosis or tumefactive demyelination) can be mistaken for tumour-like space-occupying lesions suggesting a malignant outcome.

Methods: We reviewed our own experience of multiple sclerosis subjects ( = 28) with tumefactive demyelination to determine the relationship between clinical outcomes and lesion evolution, clinical outcomes and their relationship to different therapies. Patients with central nervous system demyelinating disease were identified from our database over the last 10 years.

Myelinating Proteins in MS Are Linked to Volumetric Brain MRI Changes.

Background And Purpose: There is evidence of a relationship between promyelinating proteins and clinical multiple sclerosis (MS) activity during clinical relapse or recovery from clinical relapses. We examined the linkage between promyelinating biomarkers and volumetric changes in MS subjects during serial magnetic resonance imaging (MRI).

Methods: We enrolled 13 MS subjects with active brain MRI scans not on disease modifying therapies.

The impact of environmental enrichment on the murine inflammatory immune response.

Living in a mentally and physically stimulating environment has been suggested to have a beneficial effect on the immune response. This study investigates these effects, utilizing a 2-week program of environmental enrichment (EE) and 2 models of acute inflammation: zymosan-induced peritonitis (ZIP) and the cecal ligation and puncture (CLP) model of sepsis. Our results revealed that following exposure to EE, mice possessed a significantly higher circulating neutrophil to lymphocyte ratio compared with control animals.

Impact of Enriched Environment on Murine T Cell Differentiation and Gene Expression Profile.

T cells are known to be plastic and to change their phenotype according to the cellular and biochemical milieu they are embedded in. In this study, we transposed this concept at a macroscopic level assessing whether changes in the environmental housing conditions of C57/BL6 mice would influence the phenotype and function of T cells. Our study shows that exposure to 2 weeks in an enriched environment (EE) does not impact the T cell repertoire and causes no changes in the early TCR-driven activation events of these cells.

Ingested (oral) rituximab inhibits EAE.

Background: Blocking CD20 can inhibit autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA).

Objective: We examined whether an antibody against CD20, rituximab (RTX) (Rituxan®), used clinically in oncology, MS and RA would have similar anti-inflammatory effects in EAE after oral administration.

Design/methods: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or RTX during ongoing disease.

Ingested (oral) anti-IL-12/23 inhibits EAE.

Background: Blocking the activity of IL-12/23 can inhibit autoimmune diseases such as psoriasis.

Objective: We examined whether an antibody against IL-12/23, ustekinumab (UTZ) (Stelera®), used clinically in psoriasis would have similar anti-inflammatory effects in EAE after oral administration.

Design/methods: B6 mice were immunized with MOG peptide 35-55 and gavaged with isotype IgG control or UTZ during ongoing disease.

Massage-like stroking boosts the immune system in mice.

Recent clinical evidence suggests that the therapeutic effect of massage involves the immune system and that this can be exploited as an adjunct therapy together with standard drug-based approaches. In this study, we investigated the mechanisms behind these effects exploring the immunomodulatory function of stroking as a surrogate of massage-like therapy in mice. C57/BL6 mice were stroked daily for 8 days either with a soft brush or directly with a gloved hand and then analysed for differences in their immune repertoire compared to control non-stroked mice.

'As above, so below' examining the interplay between emotion and the immune system.

While the concept of a palpable relationship between our mental and physical well-being is certainly not new, it is only in the light of modern scientific research that we have begun to realize how deeply connected our emotional and immune states may be. We begin this review with a series of studies demonstrating how four fundamental emotional responses: anger, anxiety, mirth and relaxation are able modulate cytokine production and cellular responses to a variety of immune stimuli. These modulations are shown to be either detrimental or beneficial to a patient's health dependent on the context and duration of the emotion.

Ingested (oral) tocilizumab inhibits EAE.

Background: Blocking the activity of IL-6 can inhibit autoimmune diseases such as rheumatoid arthritis and Crohn's disease.

Objective: We examined whether an antibody against IL-6, tocilizumab (TCZ) (Actemra®), used clinically in rheumatoid arthritis (RA) would have similar anti-inflammatory effects in EAE after oral administration.

Design/method: B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or TCZ during ongoing disease.

Contrast enhanced MR venography with gadofosveset trisodium: evaluation of the intracranial and extracranial venous system.

Purpose: To demonstrate the efficacy of contrast enhanced magnetic resonance venography (CEMRV) using gadofosveset trisodium in the comprehensive evaluation of the intracranial and extracranial venous system.

Materials And Methods: Temporal signal decay, in-plane saturation and flow artifacts were assessed in an institutional review board approved, HIPAA compliant CEMRV study of 99 subjects. In a 39 subject subset, percent diameter narrowing of the internal jugular (IJ), brachiocephalic and azygous veins were coded according to the following ordinal grades for both catheter venography (CV) and CEMRV: grade 0 ≤ 50%, grade 1 >50% and ≤ 75%, grade 2 >75% and <100% and grade 3 = 100% and compared with pressure gradient measurements obtained during CV.

Chronic cerebrospinal venous insufficiency: masked multimodal imaging assessment.

Background: Chronic cerebrospinal venous insufficiency (CCSVI) was implicated in the pathophysiology of multiple sclerosis (MS).

Objective: We evaluated neurosonography (NS), magnetic resonance venography (MRV), and transluminal venography (TLV) in subsets of MS patients drawn from a single-center, prospective, case-control study of 206 MS and 70 non-MS volunteers.

Methods: As previously reported, findings on high-resolution B-mode NS imaging with color and spectral Doppler of the extracranial and intracranial venous drainage consistent with CCSVI were similar among MS and non-MS volunteers (3.

Chronic cerebrospinal venous insufficiency: case-control neurosonography results.

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) has been implicated in the pathophysiology of multiple sclerosis (MS). We sought to determine whether neurosonography (NS) provides reliable information on cerebral venous outflow patterns specific to MS.

Methods: This was a single-center, prospective case-control study of volunteer MS and non-MS participants.