Modulation of the immunoglobulin dysregulation in GvH- and SLE-like diseases by the murine IL-4 receptor (IL-4-R).
As has been reported previously, models of chronic graft-versus-host (GvH) and systemic lupus erythematosus (SLE)-like diseases are characterized by high IgE and IgG1 immunoglobulin (Ig) levels in the serum. An IL-4 induced pathological expansion of Th2 helper cells has been described for both disease models. Due to the immunopharmacological profile of soluble recombinant interleukin-4 receptor (IL-4-R) to bind specifically the corresponding ligand IL-4 and thereby to modulate biological activity upon exogenous administration in various autoimmune disease models, we investigated the immunoregulatory activity of IL-4-R and anti-IL-4 monoclonal antibody (MAb) 11B11 on the development of SLE-like disease in MRL/lpr autoimmune mice and on chronic GvH reaction in BDF1 hybrid mice. Sensitized GvH-BDF1 hybrid mice and SLE in MRL/lpr autoimmune mice were treated in vivo with the IL-4 antagonists to alter the pattern of serum Ig production and to modulate the disease process. These animals were followed for proteinuria, autoantibody production (anti-dsDNA), serum IgE, IgG1 and IgG2a levels, and the survival was monitored. Treatment of these diseased animals resulted in an improved survival rate, lowered the percentage of animals with lymphadenopathy and hepatosplenomegaly, reduced the levels of autoantibodies and inhibited proteinuria of the developing glomerulonephritis in both mouse strains, even in the established diseases. In both models the increase in total IgE and IgG1 levels in serum was strongly inhibited by the IL-4 antagonists, even under therapeutic conditions. But there was no inhibitory activity observed on the IgG2a serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany.
H U
HU
Schorlemmer
G
G
Dickneite
E J
EJ
Kanzy
K H
KH
Enssle
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000378:metabolism* / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D018123:Receptors, Interleukin / Q000276:immunology* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology
D007136:Immunoglobulins; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D015847:Interleukin-4