Interleukin 4

The interleukin 4 (IL4) is a is_associated_with::cytokine that induces differentiation of naive helper T cells (is_associated_with::Th0 cells) to is_associated_with::Th2 cells. Upon activation by IL-4, is_associated_with::Th2 cells subsequently produce additional IL-4 in a positive feedback loop. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell. It is closely related and has functions similar to is_associated_with::Interleukin 13.

Function
It has many biological roles, including the stimulation of activated is_associated_with::B-cell and is_associated_with::T-cell proliferation, and the differentiation of B cells into is_associated_with::plasma cells. It is a key regulator in humoral and is_associated_with::adaptive immunity. IL-4 induces B-cell is_associated_with::class switching to is_associated_with::IgE, and up-regulates is_associated_with::MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, and dendritic cell IL-12.

Overproduction of IL-4 is associated with is_associated_with::allergies.

Inflammation and wound repair
Tissue macrophages play an important role in chronic is_associated_with::inflammation and is_associated_with::wound repair. The presence of IL-4 in extravascular tissues promotes alternative activation of macrophages into M2 cells and inhibits classical activation of macrophages into M1 cells. An increase in repair macrophages (M2) is coupled with secretion of IL-10 and TGF-β that result in a diminution of pathological inflammation. Release of is_associated_with::arginase, is_associated_with::proline, polyaminases and TGF-β by the activated M2 cell is tied with wound repair and is_associated_with::fibrosis.

Receptor
The receptor for Interleukin-4 is known as the IL-4Rα. This receptor exists in 3 different complexes throughout the body. Type 1 receptors are composed of the IL-4Rα subunit with a common γ chain and specifically bind IL-4. Type 2 receptors consist of an IL-4Rα subunit bound to a different subunit known as IL-13Rα1. These type 2 receptors have the ability to bind both IL-4 and IL-13, two cytokines with closely related biological functions.

Structure
IL-4 has a compact, globular fold (similar to other is_associated_with::cytokines), stabilised by 3 is_associated_with::disulphide bonds. One half of the structure is dominated by a 4 is_associated_with::alpha-helix bundle with a left-handed twist. The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel is_associated_with::beta-sheet.

Discovery
This cytokine was co-discovered by Maureen Howard and William Paul and by Dr. is_associated_with::Ellen Vitetta and her research group in 1982.

The is_associated_with::nucleotide sequence for human IL-4 was isolated four years later confirming its similarity to a mouse protein called B-cell stimulatory factor-1 (BCSF-1).

Clinical significance
IL-4 also has been shown to drive is_associated_with::mitogenesis, dedifferentiation, and is_associated_with::metastasis in is_associated_with::rhabdomyosarcoma. IL-4, along with other Th2 cytokines, is involved in the airway inflammation observed in the lungs of patients with allergic asthma.