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

Abstract

Due to the immunopharmacological profile of soluble recombinant interleukin-4 receptor (IL-4-R) to bind specifically the corresponding ligand Il-4 and there-by to modulate biological activity upon exogenous administration in various autoimmune disease models, we further elucidated the disease modifying potential of IL-4-R on the development of a systemic lupus erythematosus (SLE)-like disease in MRL/lpr autoimmune mice and on a chronic graft vs. host (GvH) reaction in BDF1 hybrid mice. Treating autoimmune MRL/lpr mice, which spontaneously develop a SLE-like disease with murine IL-4-R, resulted in a decrease in the amount of autoantibodies and inhibited proteinuria of the developing glomerulonephritis. Also, an improved survival rate was observed, and at the same 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 intravenously with murine IL-4-R during the induction phase of the disease, the development of a glomerulonephritis (proteinuria) was inhibited, the increase in total IgE was strongly reduced and the survival rate was improved in this model. Even a therapeutic effect in reducing chronic GvH related symptoms was demonstrated when recombinant IL-4-R was given during the disease after the appearance of clinical signs in the hybrid mice.