aclarubicin and Anemia--Hemolytic

The immunosuppressive efficacy of the antineoplastic antibiotic Aclacinomycin A (ACM) was assayed in several test models for humoral and cellular immune response. Humoral immune response, measured as splenic plaque forming cells (PFC) in vitro and in vivo was markedly inhibited by ACM. Suppression of PFC in vivo could be observed when ACM was administered together with the antigen, or three days later. Concomitantly a decrease of circulating antibodies to SRBC was obtained. No effect on T-cell mediated immune response - DTH reaction and allogeneic cytotoxic lymphocytes - or on skin transplantation or a T-cell mediated autoimmune disease, EAE, was observed. ACM beneficially influenced the course of the disease in two GvH-models (hemolytic anemia and immune complex glomerulonephritis) which lead to a B-cell mediated autoimmune disease with fatal outcome. It was concluded that the therapeutic effect of ACM on GvH-disease is mediated via its suppression of the B-cell response.

Topics: Aclarubicin; Anemia, Hemolytic; Animals; Antibiotics, Antineoplastic; Antibody Formation; Encephalomyelitis, Autoimmune, Experimental; Female; Glomerulonephritis; Graft vs Host Disease; Hemolytic Plaque Technique; Immune Complex Diseases; Immunity, Cellular; Immunosuppressive Agents; Mice; Mice, Inbred Strains; Naphthacenes; Rats; Rats, Inbred Lew

The anti-cancer drug Aclacinomycin A (ACM) was able to inhibit the humoral immune response of mice against sheep red blood cells. This could be demonstrated in the formation of antibody secreting cells (PFC) and serum antibody titers, when ACM was administered either together with the antigen or three days after antigen application. Cellular immunity was not affected by the drug. In two murine Graft-vs-Host (GvH) disease models leading to two different B cell dependent auto-immune diseases (immune complex glomerulonephritis and immune hemolytic anemia) a protective effect of ACM was observed when it was administered at the time of the graft. The application of ACM in the induction phase mitigated the development of glomerulonephritis and prevented animals from dying due to hemolytic anemia. Only a slight therapeutical effect was observed when ACM was given after the appearance of clinical symptoms. In a T cell induced auto-immune disease (experimental allergic encephalomyelitis (EAE], ACM had no discernible effect on the course of the disease. It seems that the therapeutic effects of ACM on GvH-diseases are mediated via suppression of B-lymphocytes.

Topics: Aclarubicin; Anemia, Hemolytic; Animals; Antibiotics, Antineoplastic; Antibody Formation; Autoimmune Diseases; Body Weight; Encephalomyelitis, Autoimmune, Experimental; Female; Glomerulonephritis; Immunity, Cellular; Immunosuppressive Agents; Leukocyte Count; Male; Mice; Mice, Inbred Strains; Naphthacenes; Rats; Rats, Inbred Lew