Lung injuries caused during the progression of pulmonary fibrosis can lead to an increase in two inflammatory proteins, IL-6 and IL-33, which can trigger muscle damage and weight loss, a mouse study says.
The study, “Elevation of IL-6 and IL-33 Levels in Serum Associated with Lung Fibrosis and Skeletal Muscle Wasting in a Bleomycin-Induced Lung Injury Mouse Model,” was published in the journal Mediators of Inflammation.
The progression of pulmonary fibrosis is associated with a disregulation of the immune response, which is mediated by several mediator proteins called cytokines.
Previous reports have shown that two interleukins (IL; a type of cytokine), IL-6 and IL-33, mediate inflammation in the lungs, and are disregulated in pulmonary diseases such as pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease (COPD).
Cytokines can also activate other proteins and trigger a variety of processes, such as weight loss. In turn, weight loss caused by muscle damage is known to be associated with poor outcomes in patients with various conditions, including chronic pulmonary disease and cancer.
Now, researchers in Taiwan used a mouse model of pulmonary fibrosis to study whether this condition was associated with increased levels of IL-6 and IL-33, and whether these inflammatory cytokines could cause muscle damage.
The model was established by giving bleomycin, a medicine used to fight cancer, to the mice. Bleomycin is known to cause lung toxicity and lead to symptoms similar to those of lung fibrosis in humans.
Researchers showed that bleomycin treatment caused lung fibrosis and reduced lung function in the animals. Additionally, the mice lost up to 10% of their body weight after receiving the treatment. This weight reduction was associated with muscle damage and degradation of muscle proteins.
The researchers also noticed that the appearance of lung injuries was associated with increased levels of IL-6 and IL-33 in the blood.
The team suggested that IL-6 and IL-33 could travel in the blood and reach the muscles, where they activated other proteins that caused the degradation of muscle proteins and muscle damage.
Researchers also speculated that the cytokines caused a similar response in the adipose tissue, which would explain the weight loss seen in mice.
“Although the loss of body weight and muscle atrophy in chronic lung disease is a multifactorial event, these accumulating data suggest that both IL-6 and IL-33 are increased in [the blood] during lung fibrosis, which may synergistically cause body weight loss in mice,” the researchers said.
“Therefore, we think that attenuating the secretion of IL-6 and IL-33 from damaged lung tissue during lung injury might prevent body weight loss and skeletal muscle atrophy, thus improving the clinical outcome,” they concluded.