New research in mice has revealed that strong skeletal muscles play an important role in maintaining an effective immune system. This is particularly the case during severe chronic illnesses, which can otherwise wear the immune system down.
In addition, skeletal muscles may combat the process of cachexia. This refers to the wasting away of muscle and fat that often accompanies severe chronic illness, alongside a weakening of the immune system.
The research, which scientists at the German Cancer Research Center in Heidelberg have now published in the journal Science Advances, lays the groundwork for future studies to determine if the same is true in humans.
According to the National Cancer Institute (NCI), cachexia typically accompanies severe chronic illnesses such as cancer. It is characterized by the wasting away of the body’s muscle and fat.
Cachexia may be responsible for up to a third of cancer-related deaths. It can also affect people with other serious conditions, such as AIDS, chronic kidney diseases, and heart failure.
According to Dr. Alfred Goldberg — of the Harvard University School of Medicine in Cambridge, MA — cachexia may be due to the body overcompensating when it attempts to take energy from muscle and fat to help fight a severe illness. However, exactly why and how this happens are still largely unknown.
Despite cachexia’s link to mortality, researchers have not yet developed any effective therapies for it. However, according to the NCI, there is a growing awareness of the need to research cachexia in the hope that scientists can find effective therapies.
Alongside cachexia, people with severe illnesses can also experience a weakened immune system. This is because their T cells, which are central to the immune system’s response to illness, become exhausted.
Scientists have also linked these T cells to cachexia. According to senior study author Dr. Guoliang Cui: “It is known that T cells are involved in the loss of skeletal muscle mass. But whether and how, in turn, skeletal muscles influence the function of the T cells is still unclear.”
In this context, the researchers developed a study to explore the relationship between cachexia, skeletal muscle mass, and T cells.
First, they transmitted the lymphocytic choriomeningitis virus to mice. They then studied the gene expression in the skeletal muscle of the mice. They noticed that in response to the chronic infection, the mice’s muscle cells released more of the messenger substance interleukin-15.
Interleukin-15 attracts the precursors of T cells — in this case, to the skeletal muscle. This places these precursor T cells away from the infection that is wearing down the T cells combating the infection.
“If the T cells, which actively fight the infection, lose their full functionality through continuous stimulation, the precursor cells can migrate from the muscles and develop into functional T cells.”
– Lead study author Dr. Jingxia Wu
“This enables the immune system to fight the virus continuously over a long period,” she adds.
Significantly, the study revealed a relationship between muscle mass loss and T cell exhaustion. This has implications for the strength of the immune system.
As Dr. Cui notes: “In our study, mice with more muscle mass were better able to cope with chronic viral infection than those whose muscles were weaker. But whether the results can be transferred to humans, future experiments will have to show.”
The study focused on skeletal muscle, but cachexia also causes fat tissue to waste away. As a consequence, the study authors suggest that future research could explore whether or not a similar relationship exists between fat tissue and the protection of T cells.
The researchers also note that it is not yet clear how these T cell precursors form in skeletal muscle mass.
The hope is that as further studies answer these questions, scientists can develop effective therapies that specifically target cachexia in humans.