inflammation

A diet rich in vegetables and low in protein reduced inflammation in multiple sclerosis (MS) patients by modulating the gut microbiome and promoting bacteria that helps control a hyper-reactive immune system. The study reporting the findings, “Immunological and Clinical Effect of Diet Modulation of the Gut…

The CXCR7 receptor present on mature monocytes — a type of white blood cell — may be a therapeutic target to alleviate the inflammation seen in multiple sclerosis (MS) and similar disorders, a new study shows. The study, “Frontline Science: CXCR7 mediates CD14+CD16+ monocyte transmigration across the blood…

News commentary One particular session on Day 2 of the four-day 7th Joint ECTRIMS-ACTRIMS Meeting — which drew 10,000 researchers, doctors, industry representatives, and patient advocates to hear about advances in multiple sclerosis (MS) treatment and understanding — attracted so much interest that all seats were taken in the…

An immune signaling protein called interleukin-35 has anti-inflammatory properties that scientists might harness to develop a therapy for multiple sclerosis and other autoimmune disorders, according to two studies. Researchers at the National Eye Institute of the National Institutes of Health discovered that a subunit of interleukin 35, which is also known as IL-35, significantly reduced inflammation in mouse models of eye inflammation and multiple sclerosis. Immune B-cells produce IL-35 to communicate with, and regulate the behavior of, surrounding cells. In a previous study, the research team found that the protein could inhibit inflammation in the eyes of animals with autoimmune uveitis, or inflammation of the inner layers of the eye. An autoimmune disease is one in which the immune system attacks healthy cells instead of invaders. A drawback of trying to use a synthetic version of IL-35 as a therapy is that it's difficult to produce because of its complex structure and it's unstable in a solution. Natural IL-35 is composed of two subunits, IL-12p35 and Ebi3, which bind to create the full protein. The team wondered if they could use a subunit, instead of the full protein, as an anti-inflammatory agent. Their study, “IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease,” was published in the journal Nature Communications, They demonstrated that the IL-12p35 subunit could generate anti-inflammatory effects similar to those of the full IL-35 protein. Giving IL-12p35 to mice with uveitis promoted the expansion of immune B-cells that counteract autoimmune responses, reversing the animals' eye symptoms. In the second study, researchers discovered that the subunit tempered inflammation in a mouse model of multiple sclerosis. Giving the animals IL-12p35 every other day for up to 12 days promoted immune cell proliferation that inhibited inflammation in the mice's brains and spinal cords, improving their symptoms. The research demonstrated IL-35 and its subunit's potential to treat nerve-inflammation disorders. The team published its findings in the journal Frontiers of Immunology. The article is titled “IL-12p35 inhibits neuroinflammation and ameliorates autoimmune encephalomyelitis.” The team is now looking at IL-12p35's ability to treat other degenerative eye diseases, such as diabetic retinopathy and macular degeneration.

(Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this column about terms starting with the letter I.) Symptoms of MS Incontinence A common symptom of MS, incontinence refers to an inability to control one’s…

Probiotics may improve the health of people with multiple sclerosis (MS) by reducing disability and improving inflammatory and metabolic parameters, an Iranian study shows. Live microorganisms linked to health benefits, known as probiotics, have long been known to help chronic disease patients. In a previous study of people with major depressive disorder, probiotics treatment for eight weeks improved patients’ depression and metabolic parameters. More recently, authors investigated the impact of probiotics on a group of MS patients, looking not only at mental health and metabolic indicators, but also disability scores. Researchers at Tehran's Shahid Beheshti Hospital recruited 60 MS patients, divided them in half, and assigned 30 to take a probiotic capsule and 30 a placebo once a day for 12 weeks. The probiotic contained the healthy bacteria Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum and Lactobacillus fermentum. Researchers measured patients’ health parameters and disability scores at baseline and after treatment. The results showed that probiotic intake after 12 weeks improved MS patients' disability scores (assessed by the expanded disability status scale, EDSS) when compared to placebo controls. Although this improvement was statistically significant, it was not clinically significant — which is defined as a change of 1.0 point or more at EDSS levels less than 5.5, or 0.5 point or more at EDSS levels greater than 5.5). Moreover, benefits were also detected in several mental health parameters – Beck Depression Inventory, general health questionnaire-28 (GHQ-28), depression anxiety and stress scale. Consuming probiotic capsules also significantly decreased insulin levels and high-density lipoprotein (HDL) cholesterol in circulation, researchers also found. It also lowered certain markers of inflammation and oxidative stress, such as serum high-sensitivity C-reactive protein (hs-CRP) and malondialdehyde (MDA).

Specific gut bacteria may drive the progression of multiple sclerosis, according to a study showing that two bacterial species made the disease worse in a mouse model of MS. Researchers at the University of California, San Francisco also pinpointed a species — found in lower numbers in MS patients —…

A Phase 2b trial assessing the experimental retroviral-targeting treatment GNbAC1 in patients with relapsing-remitting multiple sclerosis (RRMS) failed to meet its primary goal of reducing brain lesions and other signs of brain inflammation within six months. But researchers at GeNeuro and Servier — the two European companies that jointly developed the drug…

Omega-3 fatty acids might reduce inflammatory processes by boosting a mechanism that cleans out dysfunctional or unnecessary proteins in a certain type of immune cells, according to a study published in the journal Autophagy. These insights indicate that omega-3 supplements might be beneficial for certain multiple sclerosis (MS) patients,…

Chronic stress and inflammation in the brain can cause multi-organ dysfunction including severe gut failure, mediated by a newly identified nerve pathway in animal models of multiple sclerosis, a Japanese study shows. MS is an autoimmune disease caused by CD4+ T-cells that cross the blood-brain barrier protecting the central nervous system. This inflames and stresses the brain and spinal cord. In previous studies, a team led by professor Masaaki Murakami of Japan's Hokkaido University showed that these cells could cross the blood-brain barrier in specific sites. These entrance sites depend on brain regional activation, which was found to be triggered by specific nerve interactions — a mechanism the team called gateway reflexes. In collaboration with other Japanese researchers and a team from Germany, the project aimed to address the potential correlation among chronic stress, brain inflammation and organ failures in MS. Using mice with MS-like disease — the experimental autoimmune encephalomyelitis model — researchers found that animals that had autoreactive CD4+ T-cells and which were exposed to stressful conditions developed severe symptoms such as gastrointestinal failure, or even death. Detailed analysis of the animals' brains showed that in stressed mice, CD4+ T-cells accumulated in two specific sites in the center of the brain around blood vessels. This event would cause inflammation around those vessels, and activation of a nerve pathway that is commonly turned off. This switch led to gut dysfunction, bleeding and failure. "These results demonstrate a direct link between brain micro-inflammation and fatal gastrointestinal diseases via the establishment of a new neural pathway under stress," Murakami, the study's senior author, said in a news release. Researchers were able to prevent gut symptoms by inhibiting inflammation in the brain or blocking the nerve pathway responsible for driving the signals from the brain to the gastrointestinal tract. "Micro-inflammation in the brain is also seen in Alzheimer's disease and Parkinson's disease," Murakamai concluded. "So it's of particular interest to investigate possible connections between brain micro-inflammations and organ dysfunctions, including those within the brain itself, in those patients."

A bacteria present in the gut, called Prevotella histicola, prevented multiple sclerosis from developing in a preclinical mouse model, found researchers at the Mayo Clinic in Rochester, Minnesota, along with colleagues at the University of Iowa. Current research suggests that alterations to the gut microbiome residing in human intestines may potentially trigger inflammatory diseases such as MS. In an attempt to identify which gut resident bacteria are capable of modulating immune responses, researchers studied cultured small pieces of intestine tissue extracted from biopsies of patients with celiac disease. The team then isolated three bacteria strains and found that one of species — P. histicola — had the capacity to suppress MS in a preclinical animal model of the disease. “This is an early discovery but an avenue that bears further study," Dr. Joseph Murray, a Mayo Clinic gastroenterologist and the study's lead author, said in a press release. "If we can use the microbes already in the human body to treat human disease beyond the gut itself, we may be onto a new era of medicine. We are talking about bugs as drugs." By investigating how P. histicola modulated immune responses to suppress MS, researchers found that bacteria decreased the expression of two pro-inflammatory cytokines – interferon-gamma and interleukin (IL)-17. Overall results show that P. histicola has immune modulatory activity and can suppress abnormal immune responses, which ultimately prevent autoimmunity. This supports the idea that maintaining a healthy microbial community within our intestines is a potential therapeutic strategy for MS. "Our work is a classic example of a bedside-to-bench and potentially back to bedside study. Recent MS microbiome studies have shown the lack of Prevotella genus in patients with the disease and an increase when patients were treated with disease-modifying drugs," said Ashutosh Mangalam, the study's first author and an assistant professor of pathology at University of Iowa's Carver College of Medicine. "And it's not just for MS, because this may have a similar modulating effect on other nervous system and autoimmune diseases."

According to a study by researchers at Cleveland's Case Western Reserve University School of Medicine, pre-existing inflammatory diseases affecting the central nervous system make mesenchymal stem cells less effective in treating multiple sclerosis. The study notes that MSCs potentially produce several signaling proteins that can regulate immune system responses as well as help tissue regenerate. Preclinical studies have shown that this can reduce brain inflammation while improving neural repair in animal models of experimental autoimmune encephalomyelitis -- an animal version of MS that is often used in laboratory studies, since it resembles the inflammation and neuronal damage seen in MS patients. Given the need for effective new MS therapies, the results will help MSCs to advance to human clinical trials. So far, results have reported good safety data, though such therapies have failed to demonstrate therapeutic efficacy. Most such trials so far have used stem cells collected from the patient, a process known as autologous transplantation — yet this may explain why MSCs have not been effective. It's possible that pre-existing neurological conditions may alter stem cells' responsiveness as well as their therapeutic activity. To see whether that is in fact the case, team members collected stem cells from the bone marrow of EAE mice. But these stem cells were unable to improve EAE symptoms, whereas stem cells collected from healthy mice retained all their therapeutic potential and improved EAE symptoms. A more detailed analysis showed that the MSCs derived from EAE animals had different features than their healthy counterparts. In addition, the team confirmed that MSCs collected from MS patients were also less effective in treating EAE animals, compared to MSCs from healthy controls. Indeed, these MSCs from patients produced pro-inflammatory signals instead of the protective anti-inflammatory ones. “Diseases like EAE and MS diminish the therapeutic functionality of bone marrow MSCs, prompting re- evaluation about the ongoing use of autologous MSCs as a treatment for MS,” the team wrote, adding that its study supports the advancement of MSC therapy from donors rather than autologous MSC therapy to treat MS while raising "important concerns over the efficacy of using autologous bone marrow MSCs in clinical trials."

A new study on rats indicates that the antidepressant Luvox promotes the production of the neuron-protecting coating that is deficient in multiple sclerosis. It also significantly decreased the severity of the animals' disease, researchers said, adding that Luvox promoted the production of the protective coating by helping stem cells evolve into oligodendrocytes, or cells that generate what is known as the myelin sheath. Patients with MS often experience anxiety and depression, with recent studies suggesting their rate of depression is three times higher than those with other long-term medical conditions. In addition to drugs targeting the underlying mechanisms of MS, such as inflammation and myelin loss, doctors often recommend that patients take antidepressants. The most common treatments they prescribe for moderate or severe depression are a class of serotonin re-uptake inhibitors that include Luvox. Few studies have looked at antidepressants' effects on animal models of MS, however. That prompted researchers to investigate Luvox's impact on both laboratory and rat models of the disease. Researchers used embryonic neural stem cells in their study. Luvox prompted laboratory stem cells to evolve into other types of cells, including neurons, oligodendrocytes, and astrocytes, which have several roles, including supporting and repairing neurons. Prozac also promoted stem cell differentiation — but at levels 10 times higher than those of Luvox. A key finding was that that Luvox significantly decreased the severity of the disease in the rats. Another important finding was that Luvox significantly reduced demyelination and immune cell infiltration in the rats' spinal cords. It also decreased the rats' expression of pro-inflammatory proteins known as cytokines. Overall, this study “demonstrated that fluvoxamine, in addition to its confirmed role in mood disorder therapy, could serve as a candidate clinical treatment for attenuating [reducing] neuro-inflammation and stimulating oligodendrogenesis in neurological diseases, particularly MS patients.”

A gene mutation may explain the uncontrolled, inflammatory immune response seen in autoimmune and chronic inflammatory diseases like multiple sclerosis, scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) report. It's a discovery that, they said, appears to be "a big step in the right direction." According to the study, published in the journal Science Immunology, alterations in the FOXP3 gene affect specific immune cells called regulatory T-cells, or Tregs. Those mutations hamper Tregs in performing a crucial regulatory role, leading to a loss of control over the immune system’s response to a perceived threat. “We discovered that this mutation in the FOXP3 gene affects the Treg cell’s ability to dampen the immune response, which results in the immune system overreacting and causing inflammation,” Ciriaco Piccirillo, the study's lead author and an immunologist in the Infectious Diseases and Immunity, Global Health Program, at the RI-MUHC, said in a news release. Tregs are known to be the immune system players responsible for keeping other immune cells under control, preventing them from attacking the host’s own tissues, while maintaining a proper immune response against harmful agents. The normal activity of Treg cells is essential for preventing excessive immune reactions. The FOXP3 gene is also well-known, and documented, to be essential for proper Treg cell function. However, the mechanisms by which FOXP3 gene is involved in Treg cell activities are still poorly understood. In the study, “Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions,” the research team — in collaboration with researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan — evaluated the impact of a FOXP3 gene mutation in autoimmunity response. Taking advantage of cutting-edge technology, the team studied samples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. Interestingly, the researchers found that this genetic variant did not reduce the number of Treg cells or the levels of FOXP3 protein. Instead, the mutation altered the way Tregs could suppress other immune cells to prevent overactivation. “What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response,” said Piccirillo. “Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions,” added Khalid Bin Dhuban, the study's first author and a postdoctoral fellow in Piccirillo’s laboratory. The team developed a compound capable of restoring Treg cells' ability to control the immune system in the presence of this specific FOXP3 gene mutation. Tested in animal models of colitis and arthritis, two chronic inflammatory diseases, the compound reduced inflammation and restored normal Treg function. Researchers now plan to develop similar drugs that may be of use in other diseases where Treg cells are known to be defective, including multiple sclerosis, type 1 diabetes, and lupus. "Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," said Piccirillo. “Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer.” “This discovery gives us key insights on how Treg cells are born and how they can be regulated,” Piccirillo added. “With this discovery, we are taking a big step in the right direction.”

Researchers at The Salk Institute have developed a way to grow vital brain cells called astrocytes from stem cells, a potential breakthrough for basic and clinical research into several diseases, including multiple sclerosis (MS). The study “Differentiation of Inflammation-responsive Astrocytes from Glial Progenitors Generated from Human Induced Pluripotent…

A cytomegalovirus infection triggers an increase in inflammatory and cytotoxic immune cells in mice with multiple sclerosis (MS), which leads to enhanced inflammation and loss of nerve-protecting myelin. The study, “Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation,” was published in the journal Scientific Reports. A cytomegalovirus (CMV) infection…

Neuroinflammation is an essential process in the development and progression of several neurodegenerative diseases, including multiple sclerosis (MS), Alzheimer’s and Parkinson’s. Researchers from the University of North Carolina School of Medicine have discovered that proteins known as NLRC4 and NLRP3 play key roles in regulating mechanisms involved in brain…

In 2004, I was diagnosed with hypothyroidism, a condition in which the thyroid is underactive and doesn’t product enough important hormones. Six years later, I was diagnosed with multiple sclerosis (MS). Naturally, I became curious as to whether a link might exist between between hypothyroidism and MS. I am…

The Brazilian government has authorized HempMeds Brasil, a unit of California-based Medical Marijuana, to import the parent company’s hemp cannabidiol (CBD) oil flagship product — known as Real Scientific Hemp Oil (RSHO) — for the management of multiple sclerosis (MS) symptoms. This is the first time Brazil’s National Health Surveillance Agency…

Paeoniflorin (PF), a herb component used in Chinese medicine, improved symptoms and reduced inflammation in a mouse model that recapitulates the human features of multiple sclerosis (MS). The study, “Paeoniflorin Ameliorates Experimental Autoimmune Encephalomyelitis via Inhibition of Dendritic Cell Function and Th17 Cell Differentiation”, appeared in the journal…

A genome-wide study has identified DNA regions associated with higher levels of circulating cytokines, small proteins that pay a role in inflammatory diseases such as multiple sclerosis (MS). Alterations in the levels and interplay of cytokines and growth factors play a key role in several inflammatory diseases, including MS. Cytokines help regulate…

MicroRNAs in the blood could serve as biomarkers to monitor the progression of multiple sclerosis (MS), as well as help identify which mechanisms are at play in each patient, such as inflammation and tissue damage, according to new research. The findings were reported in the study, “Association Between Serum…

Genetically silencing the transcription factor Nrf2 in a mouse model of multiple sclerosis (MS) results in visual deficits, inflammation of the optic nerve, and degeneration of the retinal ganglion cells (RGC), according to a study published in the scientific journal Molecular Vision.

GeNeuro recently announced that it has finished enrolling multiple sclerosis (MS) patients in the CHANGE-MS Phase 2b  study — several months ahead of schedule. The company now expects to report topline results in mid- to late autumn rather than at year’s end. “Completing enrollment in CHANGE-MS several months sooner than previously anticipated…

Scientists unraveled the 3-D structure of a key receptor linked to inflammation in multiple sclerosis (MS) — the CC chemokine receptor 2 (CCR2) receptor — when it is bound to two inhibitor molecules simultaneously. This potentially important finding, which allows scientists to see how these molecules fit together, could aid in developing better therapeutics that…

Multiple sclerosis (MS) patients now taking part in a Phase 2b clinical trial testing the efficacy and safety of the antibody GNbAC1 will be invited to continue with treatment for two more years under a planned extension study, the biopharmaceutical companies GeNeuro and Servier recently announced. Several MS therapies rely on the capacity of antibodies to…

Dr. Rebecca Coll, a young researcher at the University of Queensland Institute of Molecular Bioscience, won the 2016 Research Australia Discovery Award for her work in identifying promising anti-inflammatory compounds that are able to block the NLRP3 inflammasome — a key driver of inflammation. The discovery could greatly benefit patients with inflammatory diseases,…

Advances in brain imaging are making it possible to visualize early and ongoing events in multiple sclerosis (MS) — beginning with the first signs of inflammation caused by immune cells entering the brain. Should the new technique become available to physicians, it likely will not only allow for more precise diagnoses, but…

Dr. Daniel Reich, a researcher with the National Institutes of Health (NIH),  has been recognized for his pioneering work on brain imaging to advance both the treatment of people with multiple sclerosis (MS) and scientific understanding of the disease. Reich, a neurologist, neuro-radiologist and neuroscientist, was awarded the 2016 Barancik Prize for Innovation in MS…

Immune activity in brain membranes may be the key to determining inflammatory profiles in the brain. These profiles, in turn, are linked to levels of brain gray matter damage, and to disability, in both early and later stages of multiple sclerosis (MS). Researchers behind the study, which was presented during the Parallel…