IL-4 (Interleukin-4)

Biology and Diseases

Interleukin-4 (IL-4), is a cytokine that is a key regulator in humoral and adaptive immunity. IL-4 induces differentiation of naive helper T-cells (Th0 cells) to Th2 cells. It has many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and the differentiation of CD4+ T-cells into Th2 cells. IL-4 plays an important role in the development of allergic inflammatory responses. IL-4 controls the production of IgE, expands IL-4 producing T-cell subsets, and stabilizes effector cell functions.

Therapies

IL-4 has therapeutic potential due to its role in the development of allergic inflammatory responses. IL-4 also has shown to have promise in drug targeting for cancer. For example, PRX321 (Protox) is a targeted therapeutic toxin in which IL-4 is linked to a Pseudomonas exo-toxin, a potent substance that can destroy cancer cells. Besides brain, kidney and lung cancer, PRX321 has shown promising preclinical results in a number of cancers overexpressing IL-4 receptors, including pancreatic, ovarian, breast, head and neck, melanoma, prostate and blood cancers such as chronic lymphocytic leukemia (CLL) and Hodgkin’s lymphoma.

Unmet Need

The concentration of plasma IL-4 in healthy human subjects has yet to be defined. Thus it is difficult to understand the role that differences in IL-4 concentrations play between disease and healthy states. In addition, when experimental therapeutics are used to target and decrease IL-4, measuring their efficacy by the velocity of IL-4 decreases is hindered by lack of assay sensitivity. Furthermore, the reading range of the most sensitive ELISA is limited to less than two logs, which forces sample retesting and wastage. Thus there is great need for a highly sensitive assay that can detect the velocity of subtle changes in concentration and measure baseline concentration of IL-4 in normal subjects.

Singulex Answer

Singulex’s IL-4 assay enables the quantification of very low levels of plasma IL-4. The assay has an LLoQ of 0.28 pg/mL and a reading range of 0.12-2000 pg/mL, allowing measurement of small changes in IL-4 levels that can provide insights into therapeutic efficacy.

This assay will allow investigators to:

1. Measure the efficacy and dosing of therapeutics designed to interfere with general inflammatory and allergic responses.

2. Design more robust clinical and preclinical studies when IL-4 concentration is used as a therapeutic endpoint.

3. Understand how IL-4 levels change in patients as they transition from a healthy to diseased state.