Heightened levels of the cytokine protein IL-1 in the blood are known as a common denominator in a broad range of diseases involving chronic inflammation, including obesity, diabetes, atherosclerosis, rheumatoid arthritis and lupus. Excessive IL-1 is known to correlate with increased production by the bone marrow of aggressive immune cells, which can damage other tissues, at the expense of cells that maintain healthy blood and immune system. But whether IL-1 itself was causing these changes, or merely acting as a bystander was not clearly understood.
Now stem cell biologists at UC San Francisco have demonstrated that IL-1 itself directly transforms the blood system by driving blood stem cells (termed “hematopoietic stem cells” or HSCs) in the bone marrow to switch away from their restorative, rejuvenating role in blood renewal and toward emergency production of immune cells.
“IL-1 is a double-edged sword,” said study senior author Emmanuelle Passegué, PhD, a professor of medicine at the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. “It’s a magnificent system for responding to acute injury or infection: When you need an immune response, you need it now, and IL-1 is critical for communicating this information and stimulating the production of immune cells by the bone marrow. But leaving on this signal is not good for the health of the organism. It damages the blood system and leads to an overproduction of immune cells that contribute to chronic inflammatory disease.”
Fortunately, the researchers also demonstrate that the negative consequences of chronic IL-1 exposure on blood stem cells are rapidly reversed when the immune molecule is removed, supporting ongoing clinical attempts to use IL-1-blocking drugs to treat diseases of chronic inflammation such as cardiovascular disease, diabetes, and arthritis and even as a way to slow aging (…)
Fortunately, the researchers discovered that the negative effects of IL-1 on HSCs are short lived. When the researchers took blood stem cells from mice that had been chronically exposed to IL-1, deprived them of IL-1 for a few weeks, then transplanted them into mice whose blood marrow had been fatally damaged, the transplanted cells flourished, regenerating a normal blood system with virtually no sign of their long previous exposure to IL-1. These results support the notion that blocking IL-1’s effects on the stem cells of the bone marrow may be a potent treatment for chronic inflammation (…)
Passegué suspects that IL-1 could play a similarly double-edged role in a variety of tissues via direct reprogramming of their stem cell populations. If so, she says, reducing chronic IL-1 exposure, may be an important approach for improving stem cell health and tissue function in the context of both inflammatory disease and normal aging (…)