White blood cells are important foot soldiers in the immune system, but their numbers can be cut by health conditions or treatments like chemotherapy. Yale scientists have now discovered a molecule that can be given to quickly boost their numbers back up, to help fight off infections without antibiotics.
Neutrophils are a type of white blood cell that are among the first responders to foreign threats like bacteria, viruses or fungi. Unfortunately, their levels can drop in a condition called neutropenia, which can be the result of certain genetic conditions or a side effect of a treatments like chemotherapy. In either case, the low neutrophil counts can make infections more serious, and there are few options for boosting them.
In the new study, Yale scientists have identified a molecule that may help. Officially known as A485, and unofficially as “prohiberin,” the molecule blocks certain proteins that regulate gene expression, triggering the release of neutrophils and other white blood cells from bone marrow.
In tests in mice, A485 was found to work quickly and only temporarily, with white blood cell counts dropping back to normal by the 12-hour mark. That might sound like a disadvantage, but it’s actually a good thing, the team says.
“Currently, the main treatment for low white blood cell counts is G-CSF, or granulocyte colony stimulating factor, which is produced by the body and can be administered as a drug,” said Nikolai Jaschke, lead author of the study. “But it has a long-lasting effect, which can be harmful in some circumstances, limiting its wider clinical use. A485 is just as potent as G-CSF but less enduring.”
Next, the team tested whether this increase in white blood cells could be useful for clearing out infection. They administered chemotherapy to mice to damage their bone marrow, which would normally reduce their immune response to infection. Then, they infected the animals with the bacteria listeria, and administered A485. Sure enough, those that received the molecule were able to clear the infections more effectively, and had greater survival than the control group. The results suggest molecules like A485 could reduce our reliance on antibiotics.
“When patients develop low white blood cell counts after chemotherapy, a condition called neutropenic fever, antibiotics are the only approved therapy,” said Jaschke. “A485 could be another option.”
There’s still plenty more work to be done, however. Exactly how A485 works remains to be discovered, the team says, and it needs to be tested on other, more common infections.
The research was published in the journal Immunity.
Source: Yale University
