Brain IFN-gamma Drives MS Disease Processes, Russian Immune Factor Analysis Finds

MS brain inflammation is a result of interactions between processes in the brain and the rest of the body, with interferon-gamma (IFN-gamma) being a key player, according to a detailed analysis of cytokines in the spinal fluid and serum of MS patients.

Russia’s Kazan Federal University found that IFN-gamma activates other factors that direct T-cells and other immune cells into the brain. Their study, “Elevated Levels of Proinflammatory Cytokines in Cerebrospinal Fluid of Multiple Sclerosis Patients,” appeared in the journal Frontiers in Immunology.

Although earlier studies have attempted to map cytokines in the cerebrospinal fluid or blood of MS patients, scientists still don’t know whether the inflammation starts within the central nervous system itself, or is a consequence of immune cells migrating into the brain and spinal cord.

Researchers recruited 20 MS patients, 16 of which had relapsing MS, three secondary progressive MS, and one primary progressive MS. Seven patients had received no treatment for their condition. The group had an average Expanded Disability Status Scale score of 3.2.

The team also recruited 20 healthy volunteers as controls for serum measurements, and 20 patients with spinal hernia as controls for cerebrospinal fluid measurements.

MS patients had higher levels of several cytokines in both serum and spinal fluid. A so-called cluster analysis revealed that many of the mediators were linked, so that researchers could build maps of how they believed the factors interacted.

Levels of four cytokines were higher in both serum and spinal fluid —  factors known to attract T-cells and immune cells called granulocytes.

IFN-gamma levels were higher in the brains, but not the serum samples, of MS patients. Based on their analyses, cytokine apparently works to activate other factors, known as chemokines — that attract immune cells.

One such immune moderator is the CCL27 molecule, which has not been explored in MS before. Analyses showed that patients both with and without acquired disability had elevated levels of CCL27, but more research is needed to understand its role in MS.

Even so, brain IFN-gamma is key to disease processes in MS, with researchers suggesting it acts on glial cells in the brain called astrocytes. They, in turn, release molecules that attract T-cells and other immune cells into the central nervous system, causing the brain damage known to occur in MS.