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 recombinant sIL-4R to mice resulted in (i) prolonged survival of heterotopic cardiac allografts; (ii) decreased popliteal lymph node enlargement in response to allogeneic cells; and (iii) inhibition of IgE secretion in response to anti-IgD treatment. Transgenic mice constitutively expressing elevated levels of biologically active sIL-4R displayed prolonged cardiac allograft survival compared with control animals. However the sIL-4R transgenic mice were capable of mounting normal antigen-specific IgE responses despite the presence in serum of up to 3 micrograms/ml sIL-4R. Surprisingly, coadministration of IL-4/sIL-4R or IL-4/anti-IL-4 mAb complexes caused a superinduction of IgE secretion in anti-IgD-treated normal mice and subsequently in other IL-4-dependent biological activities. Thus, recombinant sIL-4R can not only antagonize functions mediated by endogenous IL-4, but also potentiate the biological activity of exogenously administered IL-4. These dual roles may have possible clinical implications for the recombinant molecule, as well as for natural sIL-4R immunoregulation.