Interleukin 4 (IL-4) is a pleiotropic cytokine produced primarily by activated T lymphocytes, mast cells and basophils (1-3). The sequence of human IL-4 cDNA predicts a 153 amino acid (aa) residue precursor protein containing a 24 aa residue signal peptide that is cleaved to form the mature protein (4). At the amino acid sequence level, mature human IL-4 is approximately 50% identical to mouse IL-4 and there is no species cross-reactivity between the two proteins (1, 2). Human IL-4 also shares approximately 30% amino acid sequence identity to human IL-13 and the two cytokines exhibit overlapping biological activities (5, 6). The gene for IL-4 has been mapped to human chromosome 5q, in close proximity to the genes for IL-3, IL-5, IL-13 and GM-CSF (1, 2).

IL-4 has multiple immune response-modulating functions on a variety of cell types. It is an important regulator of isotype switching, inducing IgE production in B lymphocytes. It is an important modulator of the differentiation of precursor T helper cells to the TH2 subset that mediates humoral immunity and modulates antibody production. In addition, IL-4 has also been shown to have anti-tumor activity both in vivo and in vitro (1-3).

The biological effects of IL-4 are mediated by specific cell surface receptor complexes. One type of functional IL-4 receptor complex consists of the IL-4-binding subunit (IL-4 R) and a second chain, designated the common c chain because it has also been identified as a component of the receptor complexes for IL-2, IL-7, IL-9 and IL-15 (7-9). A second type of functional IL-4 receptor complex, consisting of the IL-4 R and the more recently cloned IL-13 R , has also been proposed (10, 11).

Although IL-4 R does not bind IL-13 directly, it has been shown to complex with the low-affinity IL-13 R to form the functional high-affinity receptor complex for IL-13 (11, 12). In addition to the membrane-bound form of IL-4 R, a naturally occurring soluble form of IL-4 R has been identified in human and mouse biological fluids and in mouse cell culture supernates (13-15). Soluble IL-4 R has been to shown to bind IL-4 with high affinity in solution.