Neutralization of cytokine GM-CSF cures MS in mice
Researchers are optimistic that neutralizing the cytokine GM-CSF - granulocyte macrophage colony-stimulating factor - might halt multiple sclerosis in humans, that has been found in a mouse study The inflammatory cytokine is essential for development of the disease, explain investigators who made the discovery after eliminating other inflammatory cytokines as responsible for triggering MS.
Inflammatory cytokine for MS isolated after six years
Researchers from University of Zurich spent six years trying to identify which inflammatory molecule or cytokine that, released by a subclass of T helper cells attack the immune system to cause inflammation in the brain and spinal cord, causing autoimmune diseases like MS, rheumatoid arthritis and juvenile diabetes or type 1 diabetes.
Until now, researchers weren’t certain which T-cells lead to autoimmune disease. Through a process of elimination, the University of Zurich team narrowed it down to GM-CSF produced by a newly discovered sub-class of T-helper cells.
Professor Burkhard Becher and his team used transgenic mouse models of multiple sclerosis for the research. He notes all of the cytokines studied so far only play a minor role in causing or worsening inflammation.
"The MS-like disease could not be induced in mice without GM-CSF," says Becher. "What's more, the disease could even be cured in MS mice if the cytokine was neutralized. He adds, "GM-CSF is therefore the first T-cell cytokine that's essential for the initiation of an inflammatory reaction.”
The team also found GM-CSF delivered by T-cells activates scavenger cells that damage tissue. Without scavenger cells Becher says inflammation doesn’t happen. Neutralization of GM-CSF reversed the process he says.
Becher says the finding, published in the journal Nature Immunology, is a sign of progress, even if clinical trials that are planned at the end of the year with MS patients fail to show benefit. A clinical trial is in progress using neutralizing antibodies against GM-CSF in patients with rheumatoid arthritis.
The new study shows neutralization of the GM-CSF cytokine was able to cure MS in mice. The researchers also found they were not able to induce multiple sclerosis without GM-CSF that they discovered by eliminating other factors. Dr. Becher says the team is "extremely hopeful" the finding will help humans with the disease.
Nature Immunology (2011) doi:10.1038/ni.2027
“RORγt drives production of the cytokine GM-CSF in helper T cells, which is
essential for the effector phase of autoimmune neuroinflammation”
Laura Codarri, Gabor Gyülvészi, Vinko Tosevski, Lysann Hesske,
Adriano Fontana, Laurent Magnenat, Tobias Suter, Burkhard Becher