- A new study finds that one instance of inflammation may cause the immune system to overreact and lead to other inflammatory disorders.
- The researchers discovered that bone marrow carries the mislearned immune system memory.
- When bone marrow from a mouse with gum disease was transplanted into a healthy mouse, the second mouse developed severe arthritis.
When it comes to certain childhood illnesses and diseases we get vaccinated against, it is a great thing that our immune systems can remember their adversaries. At the same time, when the threat is generated internally, our immune systems are not always so helpful, mistakenly attacking our bodies.
A new study suggests that inflammation in the body creates a memory in the immune system that can cause it to overreact to future stimuli, triggering or worsening subsequent inflammation-based health problems.
The hypothesis follows experiments in which bone marrow from mice with gum disease was transplanted into healthy mice, after which they developed severe arthritis.
The researchers from Penn Dental Medicine hypothesize that when the first mouse develops inflammatory gum disease, changes occur in the bone marrow’s immune cell precursors.
Dr. George Hajishengallis, corresponding author of the study at Penn Dental Medicine, tells CISION PR Newswire, “Although we use periodontitis and arthritis as our model, our findings go beyond these examples.”
“This is, in fact, a central mechanism — a unifying principle underlying the association between a variety of comorbidities,” says Dr. Hajishengallis.
The findings were published in the journal Cell.
Inflammatory responses and chronic disease
Inflammation is one of the ways the immune system keeps the body healthy. Triggers such as pathogens, toxic compounds, or damaged cells cause the immune system to send out inflammatory cells to the sites under attack.
Inflammation is a critical tool for healing.
However, the immune system can also mistakenly produce an inflammatory response at times when there is a minor threat or no threat. Such chronic inflammation is the driver of a range of diseases in the heart, pancreas, brain, lungs, liver, kidney, intestinal tract, and reproductive system. Recent research suggests inflammation may be one of the factors causing Alzheimer’s disease.
If the study’s proposed connection between different types of inflammation is confirmed in humans, it could change the way in which inflammatory diseases are thought of as disparate, individual ailments.
When asked if the study suggests such a shift in perspective, Dr. Hajishengallis told Medical News Today that he believes the body may have enhanced inflammatory responses, “owing to bone marrow-based innate immune memory induced by disease A”, which may exacerbate another disease (disease B).
Human bone marrow transplants
Bone marrow — or hematopoietic stem cell — transplants are an important therapy in the treatment of diseases such as leukemia, lymphoma, some types of cancer, and immune and blood disease.
The study calls into question the role of transplants and whether they may transfer immune memory between donor and recipient.
“If the concept that maladaptive inflammatory memory can be transmitted via bone marrow transplantation to naive recipient mice is confirmed in humans,” said Dr. Hajishengallis, “then clinicians may take inflammatory memory in the bone marrow into consideration when selecting appropriate donors for hematopoietic transplantation.”
A helpful molecule
One of the findings of the study is the potential role of interleukin-1 (IL-1) signaling, a cytokine receptor that mediates inflammation in the immune system.
The researchers found that when they blocked IL-1 signaling in mice with gum disease, the immune memory in their bone marrow no longer caused arthritis when transplanted to other mice.
Hence, IL-1 may be useful in preventing misguided immune memory that triggers comorbidities.
Dr. Hajishengallis notes in Cell, “We’ve seen anti-IL-1 antibodies used in clinical trials for atherosclerosis with excellent results. It could be that it was in part because it was blocking this maladaptive trained immunity.”
Beyond atherosclerosis, Dr. Hajishengallis explained IL-1’s further potential uses.
“We cannot rule out that IL-1 may cooperate with other (as yet unidentified) molecules in inducing innate immune inflammatory memory in hematopoietic progenitors. However, the role of IL-1 signaling in our preclinical model was not redundant, and maladaptive trained immunity was blocked in its absence,” he told MNT.
“We speculate that the successful application of anti-IL-1 antibodies for the treatment of atherosclerosis (CANTOS trial) could, in part, be the result of inhibition of maladaptive innate immune training in the bone marrow,” he added.
The authors conclude that an inflammatory disease could modify trained innate immunity in the bone marrow, which could not only aggravate this pre-existing disease but also increase a person’s susceptibility to a distinct inflammatory condition.
They hope this “unified conceptual framework could also provide a platform for therapeutic interventions targeting inflammatory comorbidities.”
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