The immune molecule Interleukin-6 (IL-6) in tumors can lead to severe brain dysfunction in cancer patients, causing a lethal wasting condition known as cachexia in approximately 50 to 80 percent of cases.
Professor Bo Li from Cold Spring Harbor Laboratory (CSHL) in the US described it as "a very severe syndrome." Professor Li stated, “Most people with cancer die of 'cachexia' instead of cancer. And once the patient enters this stage, there's no way to go back because essentially there's no treatment," in the journal Nature Communications.
Role of IL-6 in Cachexia Development
Li and his team of researchers discovered that preventing IL-6 from binding to neurons in the area postrema (AP) of the brain can stop cachexia in mice. This intervention results in the mice living longer and maintaining healthier brain function.
The team of researchers suggested, "Future drugs targeting these neurons could help make cancer cachexia a treatable disease.”
In healthy individuals, IL-6 is crucial for the natural immune response. These molecules travel throughout the body, and when they detect a potential threat, they signal the brain to initiate a coordinated response. Researchers have found that cancer interferes with this process by causing an overproduction of IL-6, which then starts binding to AP neurons in the brain. Li remarked, "That leads to several consequences. One is that animals and humans alike will stop eating. Another is to engage this response that leads to the wasting syndrome.”
The researchers employed a two-pronged strategy to prevent elevated IL-6 from affecting the brains of mice. First, they used custom antibodies to neutralize IL-6. Secondly, they applied CRISPR technology to decrease the number of IL-6 receptors in AP neurons. Both methods yielded the same outcome: the mice resumed eating, halted their weight loss, and experienced longer lifespans, according to the study.
Li explained how "The brain is so powerful at regulating the peripheral system. Simply changing a small number of neurons in the brain has a profound effect on whole-body physiology. I knew there was an interaction between tumors and brain function, but not to this extent.”
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