IL-10

Salt-rich Diet Appears to Trigger Inflammation and Promote Autoimmune Disease by Impact on T-cells, Study Reports

Researchers at Yale uncovered a way that high-salt diets may trigger inflammation and possibly contribute to the development of autoimmune diseases such as multiple sclerosis (MS). Their study, “Activated Ī²-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity,” was recently published in the journalĀ Nature…

Cannabidiol Increases Inflammatory Suppressor Cells, New MS Mouse Study Shows

Non-psychoactiveĀ cannabidiol (CBD), one of the active compounds in medicalĀ cannabis, significantly reduced clinical signs of multiple sclerosis (MS)-like disease in an experimental autoimmune encephalomyelitis mouse model. Researchers found that CBD promoted the increase of inflammatory-suppressor cells calledĀ myeloid-derived suppressor cells. The findings were reported in the study ā€œCannabidiol Attenuates Experimental Autoimmune…

Oxygen Sensor Protein Can Regulate B-Cell Anti-inflammatory Response in MS, Study Shows

Oxygen sensor proteins can regulate immune B-cell activity, preventing inflammation in autoimmune disorders such as multiple sclerosis, a study reports. The research, titled ā€œHypoxia-inducible factor-1Ī± is a critical transcription factor for IL-10-producing B cells in autoimmune disease,ā€ was published inĀ Nature Communications.Ā An autoimmune disease is one in…

Low-dose Naltrexone Changes Levels of Inflammatory Proteins in MS, Study Shows

Inhibition of the neuroactiveĀ opioid growth factor (OGF) alters the blood levels of important pro- and anti-inflammatory proteins in mice with multiple sclerosis (MS)-like disease. The recognition of this regulatory response may represent a new way to monitor disease progression and treatment response in MS. These findings were reported in a study published in the journalĀ Experimental Biology and Medicine, titled ā€œModulation of the OGFā€“OGFr pathway alters cytokine profiles in experimental autoimmune encephalomyelitis and multiple sclerosis.ā€ The study was led byĀ researchers at Penn State University. Understanding the underlying mechanisms involved in MS and finding ways to tackle them is crucial for improving early diagnosis, monitoring disease progression, and patient care. For many years, researchersĀ atĀ Penn StateĀ have been focused on understanding the benefits of low-dose naltrexone and its relation with OGF in health and disease, including MS. Naltrexone is marketed with the brand name ReVia, among others. This drug is used routinely off-label to treat MS and other autoimmune diseases, as it has demonstrated toĀ it can reduce fatigue, lessen pain, and confer a general feeling of well-being to patients. Its mode of action is not fully understood, but it is known to block the interaction of the neuroactive OGF with its receptor OGFr. In addition, low-dose naltrexone and OGF were shown to prevent the proliferation of active immune cells in mice with MS-like disease. To further evaluate the role of OGF and low-dose naltrexone in MS, researchers treated mice with naltrexone and analyzed its impact on blood levels of pro- and anti-inflammatory signaling proteins (cytokines). Results showed that after 10 days, MS mice had increased levels in seven out of 10 tested cytokines. Treatment with OGF or low-dose naltrexone was found to specifically increase the levels of the pro-inflammatory IL-6 cytokine, and significantly reduce the levels of anti-inflammatory IL-10 protein. Two other pro-inflammatory proteins, TNF-Ī± and IFN-Ī³, also were found to be increased in MS mice compared to healthy animals. While TNF-Ī± levels were unaltered upon OGF or low-dose naltrexone treatment, IFN-Ī³ was reduced at 10 days, but still present at higher-than-normal levels after 20 days of therapy. To validate its findings, the team analyzed the levels of the identified signaling proteins in blood samples collected from 14 MS patients and eight non-MS volunteers. Six MS patients were undergoing treatment with Copaxone (glatiramer acetate), and four of them had relapsing-remitting MS (RRMS). Four other RRMS patients and one primary progressive MS (PPMS) patient were receiving Copaxone plus low-dose naltrexone; three RRMS patients were receiving low-dose naltrexone alone. The analysis revealed that IL-10 serum values were comparable between non-MS controls and all MS patients on low-dose naltrexone alone, or Copaxone alone. Patients treated with both Copaxone and naltrexone presented a broad range of IL-10 serum values ā€œthat were significantly different from MS subjects receiving LDN [low-dose naltrexone] only,ā€ the researchers wrote. In contrast, IL-6 cytokine was found to be significantly elevated in MS patients treated only with Copaxone compared to patients receiving low-dose naltrexone alone or together with Copaxone. ā€œThese data suggest that IL-6, a pro-inflammatory marker is very responsive to OGF and LDN therapy, and thus may be involved in other mechanistic pathways associated with the OGF-OGFr axis,ā€ the researchers wrote. "Identification of inflammatory cytokines that have expression profiles mediated by OGF or LDN [low-dose naltrexone] therapy increase our panel of potential biomarkers for MS,ā€ Patricia McLaughlin, PhD, said in a press release. McLaughlin is professor of neural and behavioral sciences at Penn State, and senior author of the study. ā€œWe hope that continued research will identify more specific cytokines and allow us to assemble a reliable panel of minimally invasive biomarkers related to the etiology and progression of MS," she added. Additional long-term human and mouse studies are needed to further evaluate if IL-6 and IL-10 are ā€œappropriate markers to monitor progression of MS,ā€ the researchers emphasized. Still, the team believes this study demonstrates that at least IL-6, IL-10, TNF-Ī±, and IFN-Ī³, together with OGF, can be useful biomarkers to monitor MS. "McLaughlin and colleagues have researched OGF signaling for several decades, and this seminal discovery of dysregulation in OGF expression in MS patients, and animal models, is very exciting and could lead to prognostic biomarkers for this autoimmune disorder," concluded Steven R. Goodman, PhD, editor-in-chief of the journal in which the study was published.

One More Small Piece of the Puzzle on the Role of Gut Micro-organisms in MS

Researchers found a significant increase in some types of gut bacteria and lower levels of an anti-inflammatory factor in untreated multiple sclerosis twins. The study offered working evidence that components of gut microbiota contribute to autoimmune diseases like MS. Researchers published their articleĀ in the journal Proceedings of the National Academy of Sciences.It was titledĀ "Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice." Our gut contains millions of good bacteria, fungi, bacteria-like archaea, and viruses that we can't live without. Although there are 300 to 1,000 species of bacteria in our gut, most of our intestines is populated with 30 or 40 species. RecentĀ increases in knowledge and technical advancements have made it possible for scientists to measure the equilibrium between different species in the gut, and analyze their influence on our health. One discovery was a link between the balance of bacteria in the intestines and autoimmune diseases like MS. A team of researchers decided to see if differences in gut microbiota play a role in MS progression and perhaps its onset. They analyzedĀ the feces of 34 identical twins, one of each who had MS and one of each who didn't. They used twins to try to reduce genetic and environmental differences' influence on the onset of the disease. All of those with MS were Caucasian andĀ had grown up with their healthy twin to adulthood. Researchers analyzed the type and abundance of microorganisms in the feces of both the MS-affected and healthy twins. They found no differences in species or amount of bacteria between siblings. What they did find was a significant increase in some types of bacteria, such as Akkermansia, in untreated twins with MS. The team transplanted fecal samples from MS-affected and healthy twins into a mice model of MS called experimental autoimmune encephalomyelitis. These animals have an inflammatory myelin-destroying disease of the central nervous system that is comparable to human MS. Myelin is a protective coating around neurons whose loss is associated with MS. MS twin-derived gut microbiota caused a significantly higher amount of mice to develop a relapsingā€“remitting autoimmunity similar to MS than healthy twin-derived microbiota. When researchers measured the microbial profiles of the mice's feces, they found significant differences in amounts of bacteria.Ā The most important difference was inĀ Sutterella, an organism that helpsĀ protect against inflammation. SutturellaĀ levels were significantly reduced in the feces of mice transplanted with MS twin-derived microbiota compared with feces from healthy twins. The team alsoĀ measured the mice's immune cells and the proteins they release. They discovered that immune cells in mice with MS-twin feces transplants produced less of the anti-inflammatory factor IL-10 than immune cells from mice colonized with healthy-twin samples. IL-10, or interleukin 10, is an important immune protein. When researchers transplanted the feces of healthy twins into the mice, then gave them an antibody that blocks the function of IL-10, they also became sick. This indicated that IL-10 may temper autoimmunity in the central nervous system. The team then measured the twins' immune blood components. They found that the healthy twin had higher quantities of IL-10 than the MS-affected one. This isĀ a complex issue in which very subtle differences of type and amount of bacteria in the gut can have considerable consequences, they added. Ā