Suppression of murine lupus erythematosus by Dactinomycin

Abstract

THE disease of the NZB × NZW/F₁ hybrid mouse (B/W) is a model of systemic lupus erythematosus (SLE), perhaps the most autoimmune of human diseases. The animals develop LE cells and anti-nuclear antibodies of various specificities, and die of a fulminating chronic glomerulonephritis at an early age¹. Abnormalities of the skin² and central nervous system³, also reminiscent of clinical SLE are present as well. Like SLE patients, many of the mice have greatly extended lifespans under treatment with corticosteroids, azathioprine or cyclophosphamide, or combinations thereof^1,4. There is a body of evidence⁵ which suggests that aberrant availability of autoantigens may be a factor in both SLE and B/W disease. Other groups have emphasised the availability of nuclear materials from keratinising skin cells as a source^6–8, but it seems to us that the nuclei from maturing erythrocytes should also be considered. All of the immunosuppressive agents mentioned above suppress erythropoiesis in mice⁹ and may also be limiting access of antigen to immune complexes. Here we show that Dactinomycin (actinomycin D), which inhibits erythropoiesis at doses which do not suppress antibody formation (ref. 9 and unpublished observations), is nevertheless an effective suppressant of B/W mouse disease.