Two cytokines involved in progressive multiple sclerosis

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. The debilitating disease can cause disability. Worldwide, there are an estimated 2.3 million people affected by it. More than one million of them are suffering from a progressive form of MS, which gets worse over time. In the past quarter century, great therapeutic advances have been made for other forms of MS. However, similar advances have not been seen in progressive MS.

The molecular mechanisms of progressive MS have not been fully understood. Now, researchers from VA Portland Health Care System and collaborators have identified two immunoregulatory cytokines implicated in progressive MS. The two cytokines, known as MIF and D-DT, appear to influence disease severity, the study suggests. These molecules represent new targets for progressive MS treatment.

The study, titled "MIF and D-DT are potential disease severity modifiers in male MS subjects," appears in the journal PNAS on September 18, 2017. Gil Benedek of VA Portland Health Care System is the first author.

MIF, or macrophage migration inhibitory factor, is a well-known cytokine that takes part in cell-mediated immunity, immunoregulation, and inflammation. Many studies have suggested MIF as a biomarker for diseases with an inflammatory component. D-DT, namely D-dopachrome tautomerase, is a newly described cytokine and is closely related to MIF.

In the present study, researchers from VA Portland Health Care System collaborated with researchers from Oregon Health & Science University, Yale University School of Medicine, and the University of California to examine the role of MIF and D-DT in progressive MS.

They found that levels of MIF and D-DT were higher in men with progressive MS in comparison with men with other forms of MS and women with MS. Furthermore, the increased MIF and D-DT levels in men with progressive MS was strongly associated with variants in the MIF gene.

To confirm the findings, the researchers conducted experiments in a mouse model of MS. The results showed that mice that lacked MIF or D-DT exhibited less severe disease.

In summary, these data imply that both MIF and D-DT may modulate the severity of progressive MS. Therefore, MIF, D-DT, or their common receptor CD74 may be targeted to treat the disease. Besides, a genetic analysis of the MIF gene may help predict which patients are more likely to have progressive MS.
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