IL2 - interleukin 2 |Elisa - Clia - Antibody - Protein

Background

Interleukin-2 (IL-2) is a key cytokine that plays a crucial role in the immune system, particularly in the activation and regulation of immune responses. First discovered in 1976, IL-2 was initially referred to as "T-cell growth factor" due to its role in the proliferation of T cells, a vital component of the immune system. IL-2 has since become recognized as one of the most important cytokines for maintaining immune homeostasis and enhancing the activity of immune cells, including natural killer (NK) cells, B cells, and T cells. Its role in immune modulation has significant implications in both health and disease, including cancer, autoimmune diseases, and infections.

Protein Structure

IL-2 is a small protein composed of 133 amino acids and has a molecular weight of approximately 15.5 kDa. Its three-dimensional structure is highly compact and globular, consisting of four alpha helices bundled together. This helical structure is stabilized by disulfide bonds that confer additional stability to the molecule. IL-2 interacts with its receptor complex through these alpha helices, enabling it to exert its biological effects.

The IL-2 receptor (IL-2R) is a multi-subunit receptor composed of three subunits: IL-2Rα (CD25), IL-2Rβ (CD122), and IL-2Rγ (CD132). The alpha subunit (IL-2Rα) is involved primarily in high-affinity binding of IL-2, whereas the beta and gamma subunits are responsible for signal transduction inside the cell. The gamma subunit is also shared by other cytokines such as IL-7, IL-9, and IL-15, which gives rise to overlapping functions between these cytokines.

Classification and Subtypes

IL-2 belongs to the common gamma-chain (γc) family of cytokines, which also includes IL-4, IL-7, IL-9, IL-15, and IL-21. These cytokines share the common gamma chain (CD132) as a part of their receptor complexes, which contributes to the similar effects they exert on immune cells.

IL-2 is classified as a T-helper type 1 (Th1) cytokine, which means that it predominantly supports the function of Th1 cells that are involved in mediating cellular immunity. While IL-2 is mainly produced by activated CD4+ T cells, it can also be synthesized by CD8+ T cells, dendritic cells, and NK cells.

Function and Biological Significance

IL-2 plays an essential role in multiple immune functions, most notably in T-cell proliferation, survival, and differentiation. Once secreted, IL-2 binds to the IL-2 receptor on the surface of T cells, leading to their clonal expansion. This process is critical for mounting an effective immune response against pathogens and tumor cells.

Additionally, IL-2 is crucial for the development and maintenance of regulatory T cells (Tregs), a specialized subset of T cells that suppress excessive immune responses and maintain immune tolerance to self-antigens. Without IL-2, the regulation of Tregs would be impaired, potentially leading to autoimmune diseases where the body’s immune system attacks its own tissues.

IL-2 also promotes the survival and function of NK cells, enhancing their ability to kill infected or transformed cells. Moreover, IL-2 supports B-cell proliferation and antibody production, further contributing to its role in humoral immunity.

In summary, IL-2 exerts pleiotropic effects on the immune system by promoting the expansion of effector cells that fight infections and tumors while also controlling immune responses through the activation of regulatory cells.

Clinical Issues

1. Cancer Immunotherapy: IL-2 has been used in clinical settings, particularly in cancer immunotherapy. High-dose IL-2 therapy has shown remarkable results in treating metastatic melanoma and renal cell carcinoma by boosting the activity of cytotoxic T cells and NK cells, which can kill tumor cells. However, high-dose IL-2 therapy is associated with significant toxicity, including vascular leak syndrome, hypotension, and organ dysfunction, limiting its use to select patients.
2. Autoimmune Diseases: Paradoxically, IL-2 has a protective role in autoimmunity by maintaining Treg cells, which suppress excessive immune responses. Low-dose IL-2 therapy has been explored as a potential treatment for autoimmune diseases such as type 1 diabetes, systemic lupus erythematosus (SLE), and rheumatoid arthritis. In these contexts, low-dose IL-2 selectively stimulates Tregs without overly activating effector T cells, thereby restoring immune balance.
3. Transplantation: IL-2 plays a significant role in graft rejection, as it promotes the activation of T cells that can attack transplanted organs. Blocking IL-2 signaling using IL-2R-targeting drugs like basiliximab and daclizumab is a common strategy to prevent rejection in organ transplantation.
4. Infectious Diseases: IL-2 has been explored in the context of chronic infections, such as HIV, where the immune system is compromised. Clinical trials have tested the use of IL-2 in HIV patients to boost immune recovery by expanding CD4+ T-cell counts. However, results have been mixed, with concerns about long-term efficacy and adverse effects.
5. Side Effects of IL-2 Therapy: While IL-2 has promising therapeutic potential, its administration can result in severe side effects, especially when used in high doses. These side effects include capillary leak syndrome, which leads to fluid leakage into tissues, and other complications like fever, fatigue, and low blood pressure. Careful management and monitoring of patients undergoing IL-2 therapy are essential to minimize these risks.

Summary

Interleukin-2 is a fundamental cytokine in the immune system, regulating the proliferation and function of various immune cells, including T cells, B cells, and NK cells. Its pivotal role in immune regulation makes it both a powerful therapeutic tool and a potential contributor to disease pathology. Clinically, IL-2 has been harnessed for cancer immunotherapy, autoimmune disease treatment, and transplantation medicine, although its use is often limited by toxicity concerns. The dual nature of IL-2 in promoting immune activation and maintaining immune tolerance highlights its complexity and underscores the need for further research to optimize its therapeutic applications.