Hu. Schorlemmer et al., IMMUNOREGULATION BY RECOMBINANT INTERLEUKIN-4 RECEPTOR (IL-4-R) OF MURINE GVH AND SLE-LIKE DISEASES IN BDF1 HYBRID MICE AND MRL LPR AUTOIMMUNE MICE/, Agents and actions, 41, 1994, pp. 30000180-30000182
Due to the immunopharmacological profile of soluble recombinant interl
eukin-4 receptor (IL-4-R) to bind specifically the corresponding ligan
d Il-4 and thereby to modulate biological activity upon exogenous admi
nistration in various autoimmune disease models, we further elucidated
the disease modifying potential of IL-4-R on the development of a sys
temic lupus erythematosus (SLE)-like disease in MRL/lpr autoimmune mic
e and on a chronic graft vs. host (GvH) reaction in BDF1 hybrid mice.
Treating autoimmune MRL/lpr mice, which spontaneously develop a SEE-li
ke disease with murine IL-4-R, resulted in a decrease in the amount of
autoantibodies and inhibited proteinuria of the developing glomerulon
ephritis. Also, an improved survival rate was observed, and at the sam
e time the percentage of animals with swollen lymph nodes was lowered
and splenomegaly was inhibited. Even in the established disease of MRL
/lpr mice, the cytokine receptor reduced the levels of autoantibodies
and the kidney malfunctions. When sensitized BDF1 mice were treated in
travenously with murine IL-4-R during the induction phase of the disea
se, the development of a glomerulonephritis (proteinuria) was inhibite
d, the increase in total IgE was strongly reduced and the survival rat
e was improved in this model. Even a therapeutic effect in reducing ch
ronic GvH related symptoms was demonstrated when recombinant IL-4-R wa
s given during the disease after the appearance of clinical signs in t
he hybrid mice.