Inflammation is a natural part of the body’s reaction to injury and infection, and is essential the body’s healing process. The term “inflammation” refers to the complex process by which the body’s innate immune system responds to harmful stimuli such as trauma, toxins and invading pathogens such as bacteria and viruses.
Circulating sentinels in the blood and in tissues are on the lookout for pathogens or tissue injury. Called DAMPs (damage-associated molecular pattern proteins) once they detect injury or pathogens, they activate the immune system to trigger a complex of choreographed reactions involving plasma proteins, blood vessels, immune effector cells and the increase of DAMP production to amplify the immune response. These immune inflammatory responses can be confined to specific tissues such as a joint, organs such as the respiratory tract, or they can launch a systemic inflammatory response involving inflammatory mediators (cytokines) circulating in the blood stream that produce widespread inflammation such as “cytokine storm.”
Essential features of the acute inflammatory response includes the activated immune system dispatching white blood cells (called leukocytes and macrophages) to migrate from the blood to the site of infection or injury in order to protect and surround the area. Another critical feature of the acute inflammatory response is inducing leakiness of blood vessels, or vascular permeability, that results in swelling and redness at the site of injury or infection. This protective process helps accommodate the influx of immune cells, reduce further damage to the tissue by limiting excessive usage, and importantly, prevent the threat from spreading throughout the body. The injured tissues and recruited cells send out DAMPs as critical signals designed to amplify the inflammatory response involving secretion of additional inflammatory mediators.
Unfortunately, while inflammation is essential to survival and wound healing, based on a variety of factors including genetics, the regulation of inflammatory processes can be corrupted. This results in excessive and sustained systemic inflammation, wreaking havoc in patients either acutely or chronically. The most devastating example of a dysregulated immune response is the unremitting inflammation associated with acute respiratory distress syndrome, or ARDS, which develops after sepsis, trauma or pneumonia from bacteria or viruses including COVID-19. The pathobiology of ARDS is characterized by massive infiltration of immune cells into the lung, sustained vascular permeability, lung flooding, severe hypoxemia and a 40% mortality rate. Currently there are no FDA-approved drugs to address this devastating critical illness.
In survivors of ARDS as well as many individuals with chronic disorders, the dysregulated immune response can also lead to persistent inflammation (months to years) as a result of genetic predisposition and ongoing environmental exposures. Persistent inflammation increases the risk of developing autoimmune diseases such as metabolic syndrome, rheumatoid arthritis, diabetes, systemic lupus, inflammatory bowel disease asthma, and other serious disorders. The body’s response to persistent inflammation in a specific organ is the development of scar tissue or fibrosis, which can occur in the heart, lung, liver, kidneys or bowel and thereby reduce organ function. Chronic inflammatory diseases contribute to more than 50% of deaths worldwide.