Interleukin-4 (IL-4)

Interleukin-4 (IL-4) is one of a group of cytokines that play a central role in the control and regulation of the immune and inflamatory systems. Specific activities associated with IL-4 are the stimulation of activated B cell, T lymphocyte, thymocyte, mast cell proliferation and the induction of cytotoxic CD8+ T cells. The latter is responsible for the antitumor activity of IL-4. Renal tumor cells that secrete large doses of IL-4 can establish tumor-specific immunity toward a preexisting renal cancer. The very potent antitumor activity of IL-4 at the primary tumour site is also associated with the elicitation of a localized inflammatory infiltrate. Further, IL-4 is responsible generating and sustaining in vivo IgE and IgG1 in the T cell-dependent immune response by causing immunoglobuilin class switching of activated B cells to igE and IdG1, respectively (IL-4 overview). In order to provide a structural basis for understanding the mode of action of IL-4 and its interaction with its cell surface receptor, the NMR assignments, secondary structure and high resolution structure of IL-4 have been determined by multidimensional NMR. The structure of IL-4 is dominated by a left-handed four-helix bundle with an unusual topology comprising two overhead connections. The linker elements between the helices are formed by either long loops, small helical turns or short strands. The overall topology is remarkably similar to that of growth hormone and granulocyte-macrophage colony stimulating factor, despite the absence of any sequence homology, and substatntial differences in relative lengths of the helices, the length and nature of the various connecting elements, and the pattern of disulfide bridges. These three proteins, however, bind to cell surface receptors belonging to the same hematopoietic superfamily, which suggests that interleukin-4 may interact with its receptor in an analogous manner to that observed in the crystal structure of the growth hormone-extracellular receptor complex.

For an updated analysis of IL-4 see the IL-13 web page.  Also, see the OM web page.

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