Researchers at Washington State University have found a brain protein that boosts the healing power of sleep and speeds an animal's recovery from the flu.
The team determined that a brain-specific protein is uniquely involved in sleep responses triggered by the influenza virus in mice. Without the protein, animals develop more severe symptoms of infection and die at higher rates than regular or control mice.
James M. Krueger, Ph.D., from WSU, said the discovery could lead to alternative treatments for influenza and other infectious diseases, possibly by using intranasal sprays to stimulate the production of the brain protein, called AcPb. Previous research indicates that sleep is necessary for a healthy immune system and plays a critical role in the body's response to bacterial and viral infections.
Dr. Krueger showed this recovery involves AcPb and interleukin-1. AcPb links up with interleukin-1 to help regulate sleep in healthy animals. It also prompts infected animals to spend more time sleeping during an illness.
In the study, mice who lacked the gene for AcPb slept less after being infected with influenza virus. They also became chilled, grew sluggish, lost their normal circadian rhythms, and ultimately died in higher numbers than the mice who slept longer.
Dr. Krueger's group findings (“The neuron-specific interleukin-1 receptor accessory protein is required for homeostatic sleep and sleep responses to influenza viral challenge in mice”) were reported in Brain, Behavior, and Immunity.
For the study, Dr. Krueger and his colleagues gave an intranasal dose of mouse-adapted H1N1 influenza virus to both regular mice and those lacking the gene for AcPb. When infected, regular mice showed the typical prolonged sleep response, but mice lacking AcPb slept less than control mice. They also developed more severe symptoms of illness and died at a higher rate.
“Body temperature and locomotor activity responses after viral challenge were lower and mortality was higher in AcPbKO [knockout] than in WT [wild type] mice,” wrote the investigators. “We conclude that neuron-specific AcPb plays a critical role in host defenses and sleep homeostasis.”
“Influenza is a lung disease,” said Dr. Krueger, “and deaths probably occur from fluid building up in the lungs. But now, we see that without AcPb in the brain, the virus is even more deadly. Why would the brain be regulating a lung disease?”
According to Dr. Krueger, scientists knew that the virus replicated in the lungs, “but we've discovered it also reaches parts of the brain, causing an inflammatory reaction involving interleukin-1 and AcPb. That reaction induces the increased sleep response that helps the body overcome an infection.”
Speculating on possible new treatments for the flu, Dr. Krueger explained that the interleukin-1-AcPb signaling complex is linked to a different molecule in the immune system called growth hormone releasing hormone (GHRH) and its receptor (GHRHR). He said GHRHR was “previously shown to be critical to the healing sleep responses induced by the influenza virus, so this may offer another potential clinical approach to treat influenza and other microbial diseases.”
While GHRH has not yet been used for treating infectious disease, other scientists are experimenting with it as a possible aid for memory and sleep, he added.