Interleukin 11 (IL-11) is a protein that acts as a messenger between cells, a type of communication molecule known as a cytokine. IL-11 was first identified in 1990 from bone marrow-derived cells and belongs to a family of cytokines that share a common signaling pathway involving a protein called gp130. This protein helps cells receive and interpret these messages, allowing IL-11 to influence diverse cellular activities.
The Primary Role of Interleukin 11
In a healthy body, Interleukin 11 plays a part in various physiological processes, most notably in the production of blood cells, a process called hematopoiesis. Its most recognized beneficial function involves stimulating the bone marrow to create more platelets, also known as thrombocytes. Platelets are small, disc-shaped blood cells fundamental for blood clotting. IL-11 achieves this by promoting the growth and maturation of megakaryocyte progenitor cells, which are the direct precursors to platelets.
Beyond its involvement in blood cell formation, IL-11 also influences bone metabolism. It promotes the differentiation of osteoblasts, cells responsible for building new bone tissue. This action supports bone formation and helps maintain bone density and strength. IL-11 also interacts with osteoclasts, the cells that break down bone, contributing to the dynamic balance of bone remodeling.
Interleukin 11 in Disease
Despite its beneficial roles, dysregulation or overproduction of Interleukin 11 can contribute to various disease states. It promotes fibrosis, the excessive formation of scar tissue in organs. This harmful process can stiffen organs like the lungs, liver, kidneys, and heart, impairing their normal function and leading to organ failure. For instance, in idiopathic pulmonary fibrosis, elevated IL-11 levels are associated with disease severity and the transformation of healthy cells into myofibroblasts, drivers of scar tissue production.
IL-11 contributes to chronic inflammation, often sustaining the inflammatory response through its activity within the supportive tissue, or stroma, of organs. It can trigger cells to transition into a more aggressive, scar-producing state, exacerbating tissue damage. This inflammatory role connects directly to its fibrotic actions, as chronic inflammation often precedes or accompanies fibrosis in many diseases.
The involvement of IL-11 extends to the growth and spread of certain types of cancer. It has been identified as a factor that can promote tumor development, including in non-small cell lung cancer and colorectal cancer. Tumor cells can induce nearby fibroblasts to produce IL-11, creating a local environment that supports cancer progression. This interaction promotes tumor growth and survival.
Medical Applications and Therapeutic Targeting
Understanding the diverse actions of Interleukin 11 has opened avenues for medical intervention, both by utilizing its beneficial effects and by countering its harmful ones. One established medical application involves the use of Oprelvekin, a manufactured version of IL-11 sold under the brand name Neumega. This medication is used to treat thrombocytopenia, a condition characterized by low platelet counts, especially in cancer patients undergoing chemotherapy. Chemotherapy often suppresses bone marrow activity, leading to a decrease in platelets and an increased risk of bleeding.
Oprelvekin works by mimicking natural IL-11, directly stimulating the bone marrow to produce more megakaryocytes and, consequently, more platelets. It is administered as a subcutaneous injection. While effective in raising platelet counts, Oprelvekin can have side effects such as fluid retention, swelling (edema), and heart rhythm irregularities like atrial arrhythmias.
Conversely, current research focuses on developing therapies that block IL-11 signaling to counteract its disease-promoting effects. This approach is being explored for the treatment of fibrotic diseases across various organs, given IL-11’s link to scar tissue formation. Researchers are developing antibodies that can specifically target and neutralize IL-11 or its receptor, aiming to arrest or even reverse fibrosis. Such blocking strategies have shown promise in preclinical models, reducing scar tissue accumulation and inflammation. This therapeutic direction also holds potential for certain cancers where IL-11 contributes to tumor growth and spread.