Long term exposure to systemic inflammation raises risk of multiple diseases, and an imbalanced immune system makes it easier for cancer to thrive
Inflammation has an important role in wound healing and reacting to injury or disease, but your immune system is a powerful thing and when it turns against you it can cause serious problems. It's abundantly clear that inflammation causes a multitude of issues as we get older, and has been connected to a huge range of processes that drive the aging process. There are a number of reasons why inflammation rises with time, such as senesecent cells which stick around and churn out inflammatory signals. A recent study even suggested that low inflammation is a better predictor of health in elderly than telomere length - although the two are likely connected (check it out here).
"Inflammation evolved to function for very short periods of time, marshaling resources to fight infections and repair damaged tissue. However, over long periods of time, these conditions become very toxic"
The latest study from Nature Cell Biology found that over exposure to the inflammatory signal interleukin-1 (IL-1) triggers stem cells in the bone marrow causes an excess of warrior and repair cells at the expense of a healthy blood cell supply. This also means an overproduction of aggressive cells that easily become rampant and cause damage to healthy tissue. Elevated levels of IL-1 are already linked to diabetes, obesity and autoimmune conditions.
What does this mean?
A skew in the blood cell production line cause by inflammatory signals means a potentially defective oxygen supply, but can also lead to a deficiency in other types of immune cells. This is bad news, as your immune system plays a crucial role in patrolling the body, scouting and snuffing out new cancers. Cancerous cells are formed all the time, but when you're young they rarely escape the immune system's watch.
IL-1 is a really important cytokine, a cell signalling molecule, and recruits cells to protect you from infection and repair injuries. When you're healthy it doesn't usually stick around very long, but we know that Il-1 levels rise with the chronic inflammation so common in old age.
"If you're working under a constant state of emergency, you become stressed and less effective. I think of blood stem cells in the same way"
A stressed out system
Being constantly 'stressed' is exhausting for hematopoietic stem cells (HSCs) in the bone marrow, the kind responsible for fielding new red and white blood cells. The study showed these cells are extremely sensitive to any environmental changes. HSCs will quickly produce quick responde myeloid cells as soon as they encounter Il-1, but if the signal continues they don't stop production. This is bad news, as it impinges on their ability to self renew and create other blood cell types. They're stressed out essentially, and don't have the time to look after themselves or ensure the blood system is balanced. Too many resources are going into creating a certain type of cell, which leaves you vulnerable to other enemies like cancer.
"They're receiving a signal telling them they need to keep building myeloid cells and as a result they don't make the other blood cells you need. You can end up with too few red blood cells, reducing the body's ability to deliver oxygen to cells. Or we see decreased production of new lymphoid cells, leaving the system potentially immunodeficient. These are all common features of chronically inflamed and even aged blood systems"
Can we repair inflamed systems?
The big question is whether HSCs exposed to IL-1 for some time are permanently changed, or whether they can recover. When the team exposed mice HSCs to raised levels of IL-1 for 20 days and then took it away, they found these cells could return back to normal. It's not yet clear whether longer exposure in human cells could be reversed in a similar way, but Il-1 blocking drugs that already exist could potentially help reduce the damage.
The researchers also suggest that bone marrow transplants that are both donor matched and checked for inflammation exposure could reverse some of these harmful changes. In the future this might even be done by expanding the patient's own cells in the lab before injecting them back in. A similar technique has already been used to combat autoimmune conditions with some success, and seems to reset the immune system.
"Blood stem cells adapt to meet what they recognize as the body's needs, and that chronic inflammation can act like a thumb on the scale, implying a need that does not really exist. Now we show that conditions in the rest of the body can have profound implications for how stem cells behave, both in the blood and likely in many other tissues as well"
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