Modulation of experimental systemic lupus erythematosus with linomide.
OBJECTIVE
The objective of this study was to assess the beneficial effects of an early administration of low dose linomide, a new immunomodulator, in an animal model of experimental systemic lupus erythematosus (SLE).


METHODS
Experimental SLE was induced in naive BALB/c mice, by immunization with anti-DNA mAb (MIV-7). Control Mice immunized with irrelevant human IgM served as controls. The immunized mice were treated with linomide (0.1 mg/ml in the drinking water), four weeks prior to the first immunization, at an early stage of the disease induction (one month after boost injection), or at a later stage (3 months following boost immunization). The treatment duration was 3 months in all schedules. The follow-up studies continued for 8 weeks after discontinuation of the treatment. The presence in the serum of autoantibodies against ssDNA, dsDNA histones, phospholipids and an irrelevant autoantigen-pyruvate dehydrogenase, was determined by enzyme-linked immunosorbent assay (ELISA). The clinical parameters assessed included erythrocyte sedimentation rate, peripheral blood cell counts and proteinuria.


RESULTS
There was a 50-64% decrease in autoantibody levels in the sera of mice immunized with anti-DNA (MIV-7) mAb at the early stage of experimental SLE in mice which received linomide for a period of 3 months. No effect of linomide was noted in mice which received the drug during the later stages of experimental SLE when the disease was fully developed. Linomide had a preventive effect on the induction of experimental SLE in naive mice, when the treatment was initiated before the induction of the disease. This effect was abolished following cessation of the treatment.


CONCLUSIONS
Linomide proved to be effective at the early stages of induction of the experimental SLE. However, the autoantibody levels rose following discontinuation of the therapy.
Zandman-Goddard
G
G
Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
George
J
J
Levy
Y
Y
Blank
M
M
Slavin
S
S
Shoenfeld
Y
Y
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000633:toxicity; D001327:Autoimmune Diseases / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D007116:Immunization, Passive; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C
D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D006912:Hydroxyquinolines; C045282:roquinimex