Interleukin-1, or IL-1, is a protein that functions as a signaling molecule, or cytokine, within the immune system. It serves as a messenger that helps regulate immune and inflammatory responses. IL-1 is one of the first signals the body produces in response to infection or injury, acting as an alarm to initiate a defensive reaction. The actions of IL-1 are a part of innate immunity, the body’s generalized defense system.
The Role of Interleukin-1 in the Immune Response
When the body detects a threat, such as invading bacteria or tissue damage, immune cells like macrophages release interleukin-1 at the site of the problem. This initiates a cascade of defensive measures, and one of its primary jobs is to start the process of inflammation to contain and eliminate the source of the trouble.
IL-1 acts as an attractant for other immune cells, recruiting them to the location of infection or injury. It increases the expression of adhesion molecules on the surface of endothelial cells, which line blood vessels. This makes the vessel walls stickier, allowing circulating white blood cells like neutrophils to stop and move into the affected tissue to clear pathogens and debris.
Another function of IL-1 is its ability to induce fever. It acts as an endogenous pyrogen, a substance produced by the body that can raise the set point of the brain’s thermostat in the hypothalamus. This increase in body temperature is a deliberate defensive strategy. A warmer internal environment can inhibit the growth of some bacteria and viruses while enhancing the function of certain immune cells.
The Two Main Forms of Interleukin-1
The interleukin-1 family has two primary forms that cause inflammation: IL-1 alpha (IL-1α) and IL-1 beta (IL-1β). Although they signal through the same receptor, their roles differ based on how and where they are produced.
IL-1α is a ‘dual-function’ cytokine that can act inside the cell or as an external signal. It is found pre-formed inside various cells and is released when a cell dies from injury or stress. This release acts as an alarm, initiating a local inflammatory response to clean up dead cells and begin repairs.
In contrast, IL-1β is the more potent, secreted form responsible for systemic effects like fever. Its production is a controlled two-step process. After being made in an inactive form, a second signal activates an enzyme that cuts it into its mature state for release. This active IL-1β travels through the bloodstream, amplifying the immune response on a broader scale.
To prevent excessive damage, the body uses a natural brake called the IL-1 receptor antagonist (IL-1Ra). This protein binds to the same receptors as IL-1 but does not activate them. This action blocks IL-1α and IL-1β from delivering their inflammatory message and helps keep the response in check.
Interleukin-1’s Connection to Disease
While the inflammatory response driven by IL-1 is necessary, the system can become dysregulated. Excessive or uncontrolled IL-1 activity can shift inflammation from a temporary, protective process into a chronic, destructive state. This sustained inflammation is the underlying cause of many autoinflammatory and autoimmune disorders.
In rheumatoid arthritis, IL-1 contributes to the joint inflammation that characterizes the condition. The cytokine promotes the breakdown of cartilage and bone, which leads to the pain, swelling, and progressive joint destruction experienced by patients.
Gout is another condition linked to IL-1. This form of arthritis is caused by uric acid crystals in the joints, which are recognized as a danger signal. This triggers a large release of IL-1β, responsible for the rapid onset of inflammation and severe pain associated with a gout attack.
There are also rare genetic disorders, such as Cryopyrin-Associated Periodic Syndromes (CAPS), where the IL-1 system is stuck in the “on” position. Due to a gene mutation, patients with CAPS produce excessive amounts of active IL-1β without any infection or injury. This results in recurrent episodes of fever, rash, and joint pain.
Beyond these diseases, chronic low-grade inflammation driven by IL-1 is also implicated in other health problems. Research suggests its involvement in conditions like type 2 diabetes and atherosclerosis, where persistent inflammation contributes to disease progression over many years.
Medical Therapies Targeting Interleukin-1
Given the role of overactive IL-1 in disease, therapies have been developed to block its activity. These drugs, known as IL-1 inhibitors or blockers, interrupt the signaling pathway of this cytokine. By doing so, they reduce the damaging inflammation associated with several chronic conditions.
These therapies often work by mimicking the body’s natural control mechanisms. Anakinra is a recombinant version of the body’s own IL-1 receptor antagonist (IL-1Ra). By introducing a higher concentration of this antagonist, the drug outcompetes IL-1α and IL-1β for binding spots on the IL-1 receptor, preventing the inflammatory signal.
Another class of IL-1 inhibitors consists of monoclonal antibodies. Canakinumab is an antibody designed to bind directly to IL-1β, neutralizing the cytokine before it can reach its receptor on target cells. By selectively targeting only the IL-1β form, these drugs can stop the systemic inflammatory cascades it triggers.
These IL-1 blocking therapies are effective in treating conditions where IL-1 plays a central role, such as rheumatoid arthritis and CAPS. For patients with these diseases, treatments targeting interleukin-1 have offered a significant improvement in quality of life by directly addressing the molecular source of their illness.