IN-VIVO BIOLOGICAL EFFECTS OF RECOMBINANT SOLUBLE INTERLEUKIN-4 RECEPTOR

We investigated the role of soluble interleukin-4 receptor (sIL-4R) as a regulator of IL-4 mediated activities in vivo. Administration of re combinant sIL-4R to mice resulted in (i) prolonged survival of heterot opic cardiac allografts; (ii) decreased popliteal lymph node enlargeme nt in response to allogeneic cells; and (iii) inhibition of IgE secret ion in response to anti-IgD treatment. Transgenic mice constitutively expressing elevated levels of biologically active sIL-4R displayed pro longed cardiac allograft survival compared with control animals. Howev er the slL-4R transgenic mice were capable of mounting normal antigen- specific IgE responses despite the presence in serum of up to 3 mu g/m l sIL-4R. Surprisingly, coadministration of IL-4/sIL-4R or IL-4/anti-I L-4 mAb complexes caused a superinduction of IgE secretion in anti-IgD -treated normal mice and subsequently in other IL-4-dependent biologic al activities. Thus, recombinant slL-4R can not only antagonize functi ons mediated by endogenous IL-4, but also potentiate the biological ac tivity of exogenously administered IL-4. These dual roles may have pos sible clinical implications for the recombinant molecule, as well as f or natural slL-4R immunoregulation.