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.

Active brain inflammation appears to be one of the causes driving anxiety and depression in patients with relapsing-remitting multiple sclerosis (RRMS), finds an Italian study published in the journal Neurology. RRMS is the most common form of the disease when patients are initially diagnosed. Multiple sclerosis patients…

Two molecules known to regulate cellular signaling contribute to the underlying mechanism of progressive multiple sclerosis, found a recent study conducted by investigators at Oregon Health & Science University and Yale University School of Medicine. These two proteins are related to each other, as they participate in the same cellular signaling process that regulate the immune system's response. Previous studies have blamed them for the worsening of several autoimmune and inflammatory disorders including rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. The research team found that patients with progressive MS had higher levels of MIF and D-DT proteins than those with the relapsing-remitting form of the disease. In addition, these proteins inflamed the central nervous system, making patients sicker. An analysis of the genes that encode the proteins revealed that higher levels of MIF were linked to the presence of two genetic variants that are more frequent in patients — particularly males — with progressive disease. Researchers confirmed their findings with animal models of MS-like disease that were genetically engineered to lack MIF and D-DT proteins. Taken together, this finding suggests that a simple genetic test could identify patients carrying the MIF genetic susceptibility — and therefore more likely to develop a severe form of MS. This study was partially funded by the National Institutes of Health, the National Multiple Sclerosis Society, the Rocky Mountain MS Center Tissue Bank and the U.S Department of Veterans Affairs.

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…

Alterations in microorganisms in the brains of multiple sclerosis (MS) patients could contribute to underlying disease mechanisms, including demyelination, according to researchers. The study, “Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis,” was published in the journal Scientific Reports. It is widely recognized that the…

Novel molecular imaging compounds that detect neuroinflammation in the brain of multiple sclerosis (MS) patients have been developed by researchers at the Washington University School of Medicine in Missouri, and may help to uncover the triggers of such inflammation and to better evaluate new disease treatments. The study, “Development and…

In a recent study entitled “Myelin oligodendrocyte glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis is ameliorated in interleukin-32 alpha transgenic mice,” a team of researchers investigated whether interleukin (IL)-32, a cytokine with an established role in rheumatoid arthritis, has a protective function in a mouse model of human multiple…

In a new study entitled “Transcription factor Nr4a1 couples sympathetic and inflammatory cues in CNS-recruited macrophages to limit neuroinflammation,” a team of scientists discovered the mechanism by which autoreactive T cells are capable of penetrating a patient’s brain and induce multiple sclerosis. The study was recently published in the advance online issue…