Chronic inflammation tricks stem cells
Researchers at the University of Colorado have found that chronic exposure to interleukin-1 – an alarm signal released under inflammatory conditions – causes hematopoietic bone marrow stem cells to produce aggressive immune cells necessary to fight infection and repair damage, to the detriment of maintaining the normal functioning of the blood system as a whole.
Interleukin-1, which belongs to the cytokine class, has long been known as an important signaling molecule used by the immune system to attract and activate pro-inflammatory cells necessary to protect the body and repair damage in acute conditions caused by infection or damage. However, an increase in the level of interleukin-1 is also characteristic of chronic inflammation accompanying aging, as well as a number of diseases associated with the so-called Western diet and lifestyle, including obesity and type 2 diabetes.
The authors explain that in conditions of chronic stress, the efficiency of a person's work decreases. Approximately the same thing happens with hematopoietic stem cells. Usually these cells are at rest in the bone marrow, periodically activated to maintain normal concentrations of blood cells. These cells are exceptionally sensitive to changes in the environment and react to these changes accordingly.
In experiments on mice, the researchers demonstrated that hematopoietic cells respond to an increase in the level of interleukin-1 by active division with the formation of myelodic cells necessary to eliminate the consequences of infection or damage. If the signal supplied by interleukin-1 does not stop, hematopoietic stem cells continue to produce predominantly myelodic cells, losing the ability to maintain a normal ratio of blood cells.
The result is the production of an excessive number of aggressive immune cells that can seriously damage tissues. At the same time, a violation of the ratio of different types of blood cells is fraught with a decrease in the efficiency of oxygen supply to tissues, the development of immunodeficiency, as well as an increased predisposition to the development of cancer.
Another important issue is the reversibility of these changes. In other words, can hematopoietic cells that have switched to hyperproduction of myeloid cells return to their normal state? This is of great importance for clinical practice, for example, in bone marrow stem cell transplantation. For many years, this approach, which consists in destroying the patient's own hematopoietic system and replacing it with stem cells from a compatible donor, has been used to treat diseases of the blood system.
However, as the results obtained by the authors have shown, in addition to the selection of tissue compatibility markers, the cells of a potential donor should be checked for chronic exposure to pro-inflammatory signals, in particular interleukin-1. Similarly, chronic inflammation in the donor's body is also an important factor in the success of the hematopoietic system after transplantation.
Separately, it should be noted the approach known as autologous stem cell transplantation, used to treat some autoimmune and malignant diseases of the blood system. It consists in isolating the patient's own hematopoietic stem cells for their subsequent return to his body after eliminating the cause of the disease with the help of chemo or radiotherapy. However, if the patient's cells have previously been chronically exposed to interleukin-1, this approach may also be imperfect, since the "damaged" cells will not be able to form a new balanced hematopoiesis system.
To test the stability of the effects of interleukin-1 on hematopoietic cells, researchers injected mice with this cytokine for 20 days. A few weeks after stopping the administration, they analyzed the condition of hematopoietic cells of animals and came to the conclusion that the effects of interleukin-1 are completely reversible.
However, they note that to date it is unclear how long it takes for human hematopoietic cells to recover and how much it depends on the duration of the interleukin-1 exposure period. It is also possible that existing clinical approaches aimed at suppressing inflammatory signals can be used to eliminate the effects of its influence.
In general, the results of the study showed how hematopoietic stem cells adapt to perform tasks that they recognize as the needs of the body, and that chronic inflammation can force them to perform unnecessary work to the detriment of overall health.
Article by Eric M. Pietras et al. Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal is published in the journal Nature Cell Biology.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Colorado Cancer Center: Chronic inflammation of obesity, autoimmune conditions leads to an imbalanced blood system and potential cancer risk.
28.04.2016