The effects of early and late administration of M-20 derived interleukin-1 inhibitor on experimental systemic lupus erythematosus.
M-20 interleukin-1 inhibitor is produced by a myelomonocytic cell line. The effects of this molecule, mediated via IL-1 inhibition, include decreased proliferative responses of mouse thymocytes, human T-cells and fibroblasts and reduction in parameters of acute inflammation. Previously, we have demonstrated the emergence of a disease resembling systemic lupus erythematosus (SLE) in naive mice immunized with anti-DNA antibodies carrying different pathogenic idiotypes. The disease was manifested by increased titers of various mouse antibodies, concomitant with the appearance of elevated erythrocyte sedimentation rate (ESR), proteinuria and leukopenia. We have applied this model of experimental SLE (immunized with MIV-7, a human monoclonal antibody) to evaluate the influence of M-20 IL-1 inhibitor, administered at different stages (2 weeks before, 1 month and 3 months following immunization) for a period of 2 weeks, on the findings of the disease in mice. It was shown that M-20 IL-1 inhibitor given 2 weeks prior to the immunization resulted in suppression of the disease induction as documented by lower antibody titer level (30%-50% in the immunized mice as compared with controls). Furthermore, reduced autoantibody levels were accompanied by other beneficial findings consisting of lower ESR, less severe proteinuria and elevated leukocyte counts. No beneficial effects of M-20 IL-1 inhibitor were observed when the agent was administered 1 or 3 months following immunization. We conclude that M-20 IL-1 inhibitor has a favorable effect on experimental SLE in mice, provided it is administered before induction of the disease.
Zandman-Goddard
G
G
Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
George
J
J
Bland
M
M
Levy
Y
Y
Yanai
P
P
Halperin
T
T
Shoenfeld
Y
Y
Barak
V
V
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000974:Antibodies, Antinuclear / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001685:Biological Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D001799:Blood Sedimentation / Q000187:drug effects; D002308:Cardiolipins / Q000276:immunology; D005260:Female; D006657:Histones / Q000276:immunology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007958:Leukocyte Count; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D010743:Phospholipids / Q000276:immunology; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology
D000906:Antibodies; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001685:Biological Factors; D002308:Cardiolipins; D006657:Histones; D007375:Interleukin-1; D010743:Phospholipids; D011768:Pyruvate Dehydrogenase Complex