A team of researchers at the David Geffen School of Medicine at the University of California-Los Angeles (UCLA) has demonstrated that the naturally occurring protein interleukin 10 (IL10) may help reduce harmful inflammation and promote muscle regeneration in people with Duchenne muscular dystrophy (DMD), and potentially those with other forms of muscular dystrophy.
MDA supported James Tidball, director of the Duchenne Muscular Dystrophy Research Center at UCLA, for this work.
About DMD molecular mechanisms
DMD is caused by the absence of dystrophin, a protein that helps stabilize muscle-cell membranes. Without dystrophin, skeletal muscles are susceptible to damage and degeneration.
In addition, inflammation produced by the immune system has been shown to be present in, and particularly harmful to, muscles affected by DMD.
Corticosteroids (such as prednisone) commonly are used in DMD and help preserve muscle strength and function. It's thought that they work, at least in part, by reducing inflammation. However, corticosteroids also cause unwanted side effects such as increased appetite, weight gain, loss of bone mass and cataracts.
About the new findings
Tidball and colleagues conducted experiments in both cell culture and in a research mouse model of DMD to determine the effects of the interleukin 10 protein on macrophages, a type of white blood cell that is a component of the immune system.
Various types of macrophages play key roles in muscle health. "M1" macrophages cause harmful inflammation leading to increased muscle damage, and "M2c" macrophages are involved in muscle repair.
The research team published its findings Feb. 15, 2011, in the journal Human Molecular Genetics. Previous research has shown that the IL10 protein regulates macrophages; one of its primary functions is to suppress the muscle-damaging M1 type and activate the M2c macrophages that stimulate muscle regeneration and repair.
To further study the balance of macrophage types regulated by IL10, the UCLA team created mice lacking the IL10 protein. Upon examination, the scientists found these mice had more active M1 macrophages, more muscle damage and less muscle strength than DMD mice with normal IL10 levels.
The researchers reported that the beneficial effects of IL10 are due to the protein's ability to influence the balance between M1 and M2c macrophages.
Meaning for people with MD
Treatment strategies that reduce inflammation appear to lessen muscle damage in DMD patients.
The authors note that IL10-based therapeutic strategies designed to reduce inflammation could prove beneficial in DMD and perhaps in other forms of MD.