The effect of cyclosporin a on early and late stages of experimental lupus

Objective. To investigate the effect of cyclosporin A (CSA) on the development of lupus in an experimental model. Methods. Lupus was induced in naive mice following injection of a human anti—double‐stranded DNA (anti‐dsDNA) monoclonal antibody carrying the 16/6 idiotype (Id). CSA was injected into the mice at an early stage of the disease (2 months after immunization) and at a late stage (4 months after immunization). Results. CSA was found to have a suppressive effect on autoantibody production, as well as on the appearance of other disease manifestations, in the mice with lupus. The effects of the drug were more prominent when the mice were treated at an early stage. This was reflected by a dramatic decrease, to normal levels, in autoantibodies to dsDNA, histones, cardiolipin, Sm, RNP, SS‐A/Ro, SS‐B/La, and anti—DNA 16/6 Id. Similar effects on the erythrocyte sedimentation rate, white blood cell count, and urinary protein levels were noted. These data were supported by electron microscopy analysis showing a lack of immunoglobulin deposition in the kidneys of mice in which treatment was started early. Conclusion. This study demonstrates that, similar to findings in other autoimmune conditions (e.g., insulin‐dependent diabetes mellitus), administration of CSA at an early stage in systemic lupus erythematosus may be more beneficial than if the drug is given at a later stage.