Therapeutic studies in NZB/W mice. IV. Effect of combination drug therapy on immune complex deposition

Azathioprine, cyclophosphamide, and methylprednisolone given individually to NZB/NZW mice retard the development of autoimmune nephritis and prolong survival in these mice. Administration of the combination of all three drugs is superior to one or two drug regimens. In the present study the kidneys of mice treated with all single, double, and triple drug regimens were compared for the degree of deposition of immunoglobulin and complement. The triple drug regimen significantly reduced overall deposition of immunoglobulin and complement compared with any other regimen. Complement and gamma2 were significantly reduced by triple drug therapy compared with any other regimen. The triple drug regimen reduced gamma1 compared with untreated and double drug treated mice. The single, double, and triple drug regimens significantly reduced gammaM deposition to about the same degree. Deposition of gammaA was not significantly reduced by any regimen. Circulating levels of these immunoglobulin classes were not reduced, a fact suggesting that the reduction in autoimmune nephritis resulting from triple drug therapy is associated with superior reduction in immune complex deposition rather than with generalized, non-specific immunodepression.