Interleukin-4 (IL-4), also known as B cell-stimulatory factor-1, is a monomeric, approximately 13 kDa-18 kDa Th2 cytokine that shows pleiotropic effects during immune responses. It is a glycosylated polypeptide that contains three intrachain disulfide bridges and adopts a bundled four alpha -helix structure. Rhesus IL-4 is synthesized with a 24 amino acid (aa) signal sequence. Mature rhesus IL-4 shares 97%, 93%, and 93% aa sequence identity with baboon, chimpanzee, and human IL-4, respectively, and 39% -50% aa sequence identity with bovine, mouse, and rat IL-4. IL-4 exerts its effects through two receptor complexes. The type I receptor, which is expressed on hematopoietic cells, is a heterodimer of the ligand binding IL-4 R alpha and the common gamma chain (a shared subunit of the receptors for IL-2, -7, -9, -15, and -21). The type II receptor on nonhematopoietic cells consists of IL-4 R alpha and IL-13 R alpha 1. The type II receptor also transduces IL-13 mediated signals. IL-4 is primarily expressed by Th2-biased CD4+ T cells, mast cells, basophils, and eosinophils. It promotes cell proliferation, survival, and immunoglobulin class switch to IgE in B cells, acquisition of the Th2 phenotype by naïve CD4+ T cells, priming and chemotaxis of mast cells, eosinophils, and basophils, and the proliferation and activation of epithelial cells. IL-4 plays a dominant role in the development of allergic inflammation and asthma.
