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/

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.