Interferon-beta: a therapeutic for autoimmune lupus in MRL-Faslpr mice.
Type I interferons are associated with lupus. Genes that are regulated by IFN-alpha are upregulated in pediatric lupus patients. Gene deletion of the IFN-alpha/beta receptor in experimental lupus-like NZB mice results in reduced disease activity. Conversely, IFN-beta is a well-established treatment in multiple sclerosis, another autoimmune disease. For determining whether IFN-beta treatment is harmful or beneficial in lupus, MRL-Fas(lpr) mice were injected with this type I IFN. Treatment was initiated in MRL-Fas(lpr) mice with mild and advanced disease. IFN-beta was highly effective in prolonging survival and ameliorating the clinical (renal function, proteinuria, splenomegaly, and skin lesions), serologic (autoantibodies and cytokines), and histologic parameters of the lupus-like disease in mice that had mild and advanced disease. Several underlying mechanisms of IFN-beta therapy involving cellular (decreased T cell proliferation and infiltration of leukocytes into the kidney) and humoral (decrease in IgG3 isotypes) immune responses and a reduction in nephrogenic cytokines were identified. In conclusion, IFN-beta treatment of lupus nephritis in MRL-Fas(lpr) mice is remarkably beneficial and suggests that IFN-beta may be an appealing therapeutic candidate for subtypes of human lupus.
Schwarting
Andreas
A
First Department of Medicine, Johannes-Gutenberg University of Mainz, Langenbeckstrasse 1, Mainz 55131, Germany. aschwart@mail.uni-mainz.de
Paul
Kathrin
K
Tschirner
Stefan
S
Menke
Julia
J
Hansen
Torsten
T
Brenner
Walburgis
W
Kelley
Vicki Rubin
VR
Relle
Manfred
M
Galle
Peter R
PR
D000818:Animals; D002455:Cell Division; D004195:Disease Models, Animal; D018450:Disease Progression; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000032:analysis; D007136:Immunoglobulins / Q000032:analysis; D007370:Interferon Type I / Q000627:therapeutic use*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008817:Mice, Mutant Strains; D011507:Proteinuria; D011994:Recombinant Proteins; D012867:Skin / Q000473:pathology; D014508:Urea / Q000097:blood
D007074:Immunoglobulin G; D007136:Immunoglobulins; D007370:Interferon Type I; D011994:Recombinant Proteins; D014508:Urea