Interleukin-4 and lnterleukin-13: Their Similarities and Discrepancies

Interleukin-4 (IL-4) and the closely related cytokine, interleukin-13 (IL-13) share many biological and immunoregulatory functions on B lymphocytes, monocytes, dendritic cells and fibroblasts. Both IL-4 and IL-13 genes are located in the same vicinity on chromosome 5 and display identical major regulatory sequences in their respective promoters, thus explaining their restricted secretion pattern to activated T cells and mast cells. The IL-4 and IL-13 receptors are multimeric and share at least one common chain called IL-4R alpha. Recent progress made in the description of IL-4 and IL-13 receptor complex have demonstrated the existence of two types of IL-4 receptors: one constituted by the IL-4R alpha and the gamma c chain, and a second constituted by the IL-4 R alpha and the IL-13R alpha 1 and able to transduce both IL-4 and IL-13 signals. Specific IL-13 receptors are results from the association between the IL-4R alpha and the IL-13R alpha 2 or between two IL-13R alpha. Furthermore, similarities in IL-4 and IL-13 signal transduction have been also described, thus explaining the striking overlapping of IL-4- and IL-13-induced biological activities such as regulation of antibody production and inflammation. However, the restricted expression of IL-4 to type 2 helper T lymphocytes as well as the inability of IL-13 to regulate T cell differentiation due to a lack of IL-13 receptors on T lymphocytes represent the major differences between these cytokines. This would indicate that although IL-4 and IL-13 share a large number of properties, precise mechanisms of regulation are also present to guarantee their distinct functions.