Liposomal clodronate as a novel agent for treating autoimmune hemolytic anemia in a mouse model.
Autoimmune hemolytic anemia (AIHA) is a disease in which autoantibodies against red blood cells (RBCs) lead to their premature destruction. Most clinically significant autoantibodies are of the immunoglobulin G (IgG) type, which leads primarily to the uptake and destruction of RBCs by splenic and hepatic macrophages. Therapies such as corticosteroids and splenectomy are directed at interfering with this process. Liposomally encapsulated clodronate (dichloromethylene diphosphonate) has previously been found to be a potent antimacrophage agent. It selectively depletes animals of macrophages within 24 hours of administration by inducing apoptosis in these cells. Therefore, we hypothesized that liposomal clodronate would be a useful agent for treating AIHA. We tested this hypothesis in a mouse model of AIHA in which animals were given either anti-RBC antibodies or preopsonized RBCs. In either case, liposomal clodronate substantially decreased RBC destruction. This drug formulation was effective within hours by first blocking and then depleting phagocytic macrophages, and its action lasted for 1 to 2 weeks. Thus, in AIHA, liposomal clodronate therapy may act like a temporary, medicinal splenectomy. As such, it may prove useful in situations where rapid response to therapy is critical or other medical therapies are inadequate.
Jordan
Michael B
MB
Department of Immunology, and the Howard Hughes Medical Institute, National Jewish Medical and Research Center, Denver, CO 80206, USA. jordanm@njc.org
van Rooijen
Nico
N
Izui
Shozo
S
Kappler
John
J
Marrack
Philippa
P
D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy*; D000818:Animals; D000911:Antibodies, Monoclonal; D004002:Clodronic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004912:Erythrocytes / Q000276:immunology; D008081:Liposomes / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D023421:Models, Animal; D010587:Phagocytosis / Q000187:drug effects; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D008081:Liposomes; D004002:Clodronic Acid