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.
Immunex Research and Development Corporation, Seattle, Washington 98101.
C R
CR
Maliszewski
T A
TA
Sato
B
B
Davison
C A
CA
Jacobs
F D
FD
Finkelman
W C
WC
Fanslow
D000818:Animals; D006085:Graft Survival; D016027:Heart Transplantation; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins
D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D015847:Interleukin-4