Inhibition of Red Cell Sequestration by Cortisone* by Manuel

More than a decade ago it was recognized that ACTH and cortisone ameliorate some hemolytic anemias in man (1-6). Nevertheless, the mechanisms responsible for their therapeutic effect have not been elucidated. I t is generally believed that cortisone and its analogues benefit only those hemolytic anemias in which the red cells can be agglutinated by Coombs (antiglobulin) serum. Indeed, of the many published case reports (7, 8) there is but one well documented study (9) indicating that cortisone administration may benefit a "Coombs-negative" hemolytic disease, hereditary spherocytosis. Agglutination of red cells by Coombs serum indicates the presence of protein, usually a globulin, attached to the cell surface. Although it has been demonstrated that red cells may be agglutinable in Coombs serum as a result of the non-immunologic adherence of protein (10--13), it is probable that the globulins attached to red cells in most cases of "Coombs-positive" hemolytic anemia are specific antibodies directed against either exogenous haptens such as drugs (14, 15) or endogenous stromal antigens (16-19). This adherence of antibody to red cells may provoke hemolysis in vivo by causing complement fixation thereby resulting in direct cellular damage (20), or more often indirectly by causing red cell sequestration and destruction in the spleen or liver (21, 22). Theoretically, cortisone might suppress the injurious effects of antibodies on red cells in the following ways: (a) By decreasing the synthesis of antibody (23, 24), (b) by interfering with antigen-antibody union (25, 26), and (c) by inhibiting the consequences of this union (27-29). In the past each of these has been invoked to explain the salutary effects of steroid therapy in acquired hemolytic anemia. Recently we have attempted to define the role of reticnloendothelial function in erythroclasia. Rats were injected with a variety of "reticnloendothelialblocking" substances in an effort to modify the sequestration of red cells previously altered in vitro by sensitization with antiserum or by prolonged sterile