Using histamine (H1) antagonists, in particular atypical antipsychotics, to treat anemia of chronic disease via interleukin-6 suppression

Abstract

Anemia of chronic disease (ACD) is a condition of decreased red cell mass secondary to some other chronic inflammatory condition. In ACD total body iron stores are normal, though serum iron is typically low secondary to iron sequestration by macrophages, and often iron supplementation is not an effective treatment for ACD for the same reason. The pathogenesis of ACD had been poorly understood, but recently there has been important progress: upregulation of interleukin-6 (Il-6) secondary to the underlying chronic inflammatory disease upregulates expression of the protein hepcidin. Upregulation of hepcidin causes anemia by a number of mechanisms: decreased intestinal absorption of iron from the duodenum, increased sequestration of iron by macrophages. Thus, downregulation of Il-6 may represent a most important treatment avenue for ACD. Anti-Il-6 antibodies might be a way to lower Il-6 levels, but such antibodies besides being expensive would have to be given intravenously or intramuscularly, and such large immunogenic molecules may not be appropriate in patients already with a chronic inflammatory condition. Here, we note that an immediately available and potentially effective treatment for ACD is to decrease Il-6 levels by histamine (H1) receptor antagonism, given that histamine acting through the H1 receptor is known to be a potent positive regulator of Il-6. Among the classes of medications that are H1 antagonists we point out that atypical antipsychotic medications such as olanzapine and quetiapine are among the most potent H1 antagonists, and can have simple daily dosing schedules and thus may be particularly useful in ACD.